Episode 106: Francisco Gonzalez-Lima talks about brain metabolic mapping and Alzheimer’s
Our guest today is Dr. Francisco Gonzalez-Lima, a professor in the department of psychology, pharmacology and toxicology and the department of psychiatry at The University of Texas at Austin. He also is a professor at the university’s Institute for Neuroscience.
We covered so much ground in our discussion with Francisco that we have split his interview into two parts. Today’s interview focuses on Francisco’s fascinating background as a youth and Cuban expatriate as well as his early research into Alzheimer’s Disease and brain metabolic mapping. The second part of our interview, which follows in a few weeks, covers two interventions Francisco has been exploring with the aim of protecting people against neurodegeneration: low-dose methylene blue and the application of near-infrared light.
Francisco describes himself as a behavioral neuroscientist. He and his colleagues at the Gonzalez-Lima Lab are recognized as world leaders for their research on the relationship between brain energy metabolism, memory and neurobehavioral disorders.
Although he has spent most of his academic career at the University of Texas, Francisco has been a visiting neuroscientist in Germany, England, Canada and Spain, and has delivered more than 120 lectures around the world about his brain research. He also has contributed work to more than 300 scientific publications.
Over the years, Francisco’s brain research has focused on transcranial lasers, memory enhancement, neuroprotection and neurocognitive disorders. Current research in the Gonzalez-Lima laboratory focuses on the beneficial neurocognitive and emotional effects of noninvasive human brain stimulation in healthy, aging and mentally ill populations. This research primarily uses transcranial infrared laser stimulation and multimodal imaging.
Show notes:
[00:03:23] Dawn opens the interview mentioning that Francisco was born in Cuba where his father worked as a veterinarian. Dawn asks how Francisco’s family ended up leaving Cuba for Costa Rica when he was only ten years old. [00:04:25] Ken asks if it is true that Francisco got into a lot of fights as a child. [00:05:19] Francisco talks about his time as a child accompanying his veterinarian father to take care of cattle. [00:06:46] Dawn asks about Francisco’s time in college, two years of which he spent in Venezuela, and how he became known as an anti-communist student leader on campus. [00:08:18] Francisco tells the story of how he ended up going to school at Tulane University. [00:09:13] Dawn mentions that because Francisco’s father was a veterinarian, Francisco went to Tulane with the intent of working with animals. But after watching a professor dissect a human brain in class one day, Francisco changed his major. [00:10:17] Ken asks Francisco what lead him to decide to get a bachelor’s degree in biology and psychology. [00:11:49] Dawn asks about Francisco’s work with Nobel Prize winner Dr. Andrew Schalley during Francisco’s last summer at Tulane. [00:12:56] Francisco explains how he ended up of the University of Puerto Rico getting his doctorate in anatomy and neurobiology. [00:14:28] Dawn asks Francisco how learning about electrophysiology in his doctoral studies had an impact on him. [00:15:22] Francisco tells an interesting story of his doctoral dissertation. [00:16:21] Dawn asks about Francisco’s work with Dr. Walter Stiehl and the papers the two of them published in the European Journal of Pharmacology. [00:17:19] Dawn mentions that in 1981 Francisco met Henning Scheich, a German professor who had done a study involving the newly developed 2-deoxyglucose autoradiographic method. Francisco talks about why this neuroimaging approach to brain research fascinated him and led him to propose an ambitious collaborative research project with Dr. Scheich. [00:18:27] Dawn asks Francisco to talk about the work he did with Dr. Scheich to develop the human FDG (fluorodeoxyglucose) neuroimaging method, the first functional brain imaging technique to be used in humans. [00:19:58] Ken asks Francisco to explain the difference between functional studies and imaging studies. [00:21:18] Dawn asks about how Francisco met a group of Texas professors at a conference in Madrid, which lead him to join the new College of Medicine at Texas A&M. [00:22:35] Dawn mentions that in 1991, the University of Texas at Austin recruited Francisco to join its new Institute for Neuroscience and the Department of Psychology. [00:23:32] Dawn asks about the research Francisco and his colleagues are doing in the Gonzalez-Lima lab. [00:24:11] Ken asks what Francisco means when he describes himself as a behavioral neuroscientist. [00:25:13] Dawn asks about Francisco’s work on the neuroimaging effects of Pavlovian conditioning. [00:27:45] Dawn asks about the work Francisco did on habituation and sensitization. [00:29:57] Ken mentions that the brain is designed to handle large amounts of communication and computation. He asks if Francisco can elaborate on this concept. [00:31:10] Ken asks Francisco to describe the redundant structures of the brain. [00:33:35] Dawn turns the discussion to Alzheimer’s Disease, mentioning we still don’t fully grasp how the brain works. [00:35:12] Dawn mentions that in 2001 Francisco published a paper titled “Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer’s Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration.” The main histochemical finding of this study was that the decreased ration or the gravity of Alzheimer’s Disease was not related to any of the other things that were commonly mentioned like amyloid or tau proteins. Francisco gives an overview of this study and its significance. [00:39:32] Ken asks if ketone uptake in the brain diminishes some cases of Alzheimer’s or TBI. [00:41:18] Ken mentions Steven Cunane’s STEM-Talk interview and the work he has done work using neuroimaging to see if it’s possible to replace the energy lost from the glucose deficit with exogenous ketones. [00:42:11] Ken asks about the early signs of Alzheimer’s Disease. [00:45:27] Ken asks about the vascular hypothesis of Alzheimer’s Disease. [00:48:16] Dawn mentions that in the past few years, there has been a lot of coverage in the media about Early Onset Alzheimer’s Disease. She goes on to say that Francisco has pointed out in past interviews that EOAD is a rare genetic disease that is causally different than the most common geriatric dementia that is mistakenly called Alzheimer’s or late onset AD. Francisco discusses how this confusion has been an obstacle in advancing research. [00:52:24] Dawn gives a preview of part two of our interview with Francisco, which will upload in a few weeks.Links:
Episode 105: Art De Vany talks about healthspan, lifespan and healing the wounds of aging
Our guest today is Dr. Arthur De Vany, who we interviewed three years ago on episode 30 of STEM-Talk. Art, who is perhaps best known as one of the founders of the Paleo movement, is the author of “The New Evolution Diet: What Our Paleolithic Ancestors Can Teach Us About Weight Loss, Fitness and Aging.”
Art is a professor emeritus of economics at the University of California, Irvine. In our first interview, we talked to Art about his early research into the economics of the movie business and how he created mathematical and statistical models to precisely describe the motion-picture market.
In today’s interview, Art talks to us about the new book he’s working on that’s tentatively titled, “The Youthful Brain—A Revolutionary Program to protect the Brain, Extend Youthfulness and Prevent Alzheimer’s Disease.”
The book is a continuation of Art’s ongoing study of the human body and brain and offers his strategies for preventing brain deterioration and maintaining a healthy, lean body.
Show notes:
[00:03:13] Dawn opens the interview mentioning that it has been three years since Art’s first appearance on the podcast. She asks Art what it is about the modern Western lifestyle that sends so many people to an early grave. [00:05:42] Dawn asks about Art’s discovery that the world’s healthiest, long-living individuals typically have low insulin. [00:07:44] Ken mentions that Art is working on a new book that will look at brain-body signaling and provide strategies for preventing brain deterioration and maintaining a healthy lean body. Art talks about how we originally planned to write about aging, but that most aging research is bull and that nobody really understands what it is. He explains that in his mind aging is basically a directed random walk into entropy. [00:10:11] Ken asks about one of Art’s key points, that Alzheimer’s disease and many other diseases of neural degeneration and cognitive decline are largely metabolic diseases compounded by loss of muscle mass and stem-cell exhaustion. [00:13:09] Dawn asks about the evolution of the human brain, and how the most recent additions to the brain are the most dependent on glucose metabolism. [00:14:22] Dawn mentions that synapses are essential to neuronal function, as they are the means by which neurons communicate signals. She asks Art to expand on the comment he made in his recent lecture at IHMC stating that “synapses are forever young but in ever need of support and protection.” [00:16:29] Ken asks about the lactate shuttle hypothesis, which is based on the observation that lactate is formed and utilized continuously in diverse cells under both anaerobic and aerobic conditions. [00:18:51] Dawn mentions the role of mitochondria, and how when they are not working the way they should that cells and tissues of our body become starved for energy, forcing us to rely on anaerobic metabolism. This results in a number of issues. She asks Art what we can do to maintain healthy mitochondria over our lifespan. [00:21:25] Art gives advice for reprograming the metabolism of the aging brain. [00:22:35] Ken asks about mTOR from an evolutionary perspective and why people have so many concerns regarding its role in cancer and degenerative disease. [00:24:35] Art explains his view of aging as the “failure of a renewal program,” and why aging is not programmed. [00:26:35] Dawn mentions that she has heard that Art eats just two meals a day, an early breakfast and dinner, to create a long interval between meals so his body can maintain low-insulin signaling. She asks how this brings on the defensive and repair pathways. [00:28:52] Ken asks about Art’s exercise routine and why he prefers fasted exercise. [00:30:46] Dawn asks about the importance of sleep, if Art still takes melatonin to help with his sleep, and what advice he has for people in terms of getting good sleep. [00:32:56] Dawn mentions that Art has commented that physically and genetically we are built to run fast and climb trees, but given the state of the modern world she asks what is the best way to stay physically fit if we are not allowed to regularly do those things that we evolved to do. [00:35:47] Ken asks for Art’s thoughts on why we have seen the loss of mass in the human brain, particularly in the hippocampus. [00:41:44] Ken asks about the role of oxytocin in preserving brain mass. [00:43:02] Dawn points out that Art is 82 years old. If aging is indeed a random walk into entropy, she asks Art what he considers a reasonable expectation is in terms of human lifespan. [00:43:50] Dawn mentions that Art has in the past said that he was 78 years old when he first started thinking about aging. Given that most people start having those thoughts in their 60s, she asks why it took him so long. [00:44:55] Ken closes the interview asking Art what advice he would give to his younger self.Links:
Episode 104: Katherine Eban talks about the dangers associated with relying on generic drugs manufactured overseas
Today’s interview is with Katherine Eban, an investigative journalist who uncovered the widespread fraud that goes on overseas in the manufacturing of U.S. generic drugs.
With the outbreak of the deadly coronavirus, which originated in China but is now spreading across the globe and United States, today’s interview is especially timely. Katherine’s recent book, “Bottle of Lies,” reveals that nearly 80 percent of the active ingredients of all brand-name and generic drugs as well as almost all of our antibiotics in the U.S. are made outside of the country, mostly in China and India. Today’s interview highlights the dangers Americans face in outsourcing the quality and safety of its brand-name and generic drugs to overseas manufacturers.
Katherine is an investigative journalist who has written award-winning stories that range from pharmaceutical counterfeiting to gun trafficking to even coercive interrogations by the CIA. Her first book, “Dangerous Doses: A True Story of Cops, Counterfeiters and the Contamination of America’s Drug Supply,” was named one of the Best Books of 2005 by Kirkus Reviews.
“Bottle of Lies: The Inside Story of the Generic Drug Boom” is a New York Times bestseller that came out in 2019 and was named one of the top 100 notable books of 2019 by the Times.
Show notes:
[00:03:16] Dawn opens the interview mentioning Katherine’s appearance on Peter Attia’s podcast. [00:04:30] Ken asks how Katherine how she ended up living just three subway stops from where she grew up in Brooklyn. [00:05:01] Katherine talks about how despite her talent and interest in writing, she at one point joined the circus in high school and considered going to clown school after she graduated. [00:06:02] Dawn asks how Katherine ended up in Rhode Island to attend Brown University instead of going to Florida to attend the Ringling Brothers Clown College. [00:06:47] Katherine talks about her time at Brown University editing the school’s literary magazine. [00:07:24] Ken Asks about Katherine’s time at Oxford University as a Rhodes scholar. [00:08:37] Dawn asks how Katherine, a woman who holds a Master’s degree in 17th Century English Epic Civil War Poetry, became a journalist. [00:10:23] Dawn asks about Katherine’s first big story, which also happened to be her first story. [00:11:49] Dawn asks Catherine long she worked at the New York Times. [00:13:07] Katherine explains how she came to write her first book, “Dangerous Doses: A True Story of Cops, Counterfeiters and the Contamination of America’s Drug Supply.” [00:14:56] Dawn mentions that after the publishing of “Dangerous Doses,” Katherine spent a decade investigating the generic-drug industry, an investigation sparked by a phone call from a colleague who asked for her help. [00:16:17] Ken asks about the difference between a generic and brand-name drug, and what is involved in the process of reverse-engineering a drug. [00:17:43] Dawn asks about the series of interviews Katherine conducted with patients sharing their experiences with generic drugs, which led to a story she wrote for “Self” magazine in 2009. [00:20:15] Ken mentions that in the “Self” magazine article, Katherine wrote about Dr. Kesselheim, an instructor at Harvard Medical school who reviewed data from 47 clinical studies. He found no evidence that patients on brand-name cardiovascular drugs had outcomes superior to those on generics. Given this study is now 10 years old, Ken asks if anyone has revisited this analysis. [00:21:25] Katherine tells the story of her anonymous informant that contacted her about a month after the “Self” magazine article, who went by the pseudonym “4 Dollar Refill.” [00:22:38] Dawn mentions that over the following five years, Katherine wrote a series of articles about generic-drug quality, which culminated in a 10,000-word article titled “Dirty Medicine” published in Fortune Magazine in 2013. [00:24:03] Dawn mentions that a reason that generic drugs account for 90% of the drugs in the U.S. is that generics are so much cheaper than brand names. She goes on to ask about how in “Bottle of Lies” Katherine explains why the low cost of manufacturing in India and China has created issues for the American consumer. [00:25:08] Dawn asks about the Carnegie Fellowship Katherine received in the midst of working on “Bottle of Lies.” [00:26:42] Ken asks Katherine how many interviews she had to do for her book. [00:27:11] Katherine talks about how the plan to help Africa during the AIDS epidemic laid the groundwork for some of the corruption she laid out in “Bottle of Lies.” [00:29:14] Katherine tells the story of Harry Lever, a cardiologist at the Cleveland Clinic, who started noticing his patients suffering from low platelet count after taking heparin, which raised his concerns, and led him to discover that heparin had been contaminated in China. [00:30:10] Ken asks what the average person can expect if they tell their pharmacist that they do not want the generic version of a drug that their doctor prescribed. [00:31:26] Dawn asks if this problem is being substantially driven by insurance companies. [00:31:56] Ken asks what it was that caused generic drugs to make up 90% of the drug supply today, when in 2009 they only made up 60%. [00:33:16] Dawn asks about Peter Baker, a young FDA investigator, who ended up in New Delhi looking into Indian drug manufacturers. [00:34:17] Ken asks about the obstacles Peter Baker faced. [00:36:47] Katherine explains what the protocol is when an FDA investigator finds contamination. [00:38:18] Dawn asks about Peter Baker’s investigation into the Wockhardt plant. [00:41:22] Ken asks Katherine to tell the story of Ranbaxy, India’s largest drug company. [00:44:27] Katherine how Dinesh Thakur became a whistleblower. [00:45:51] Ken asks what happened to Ranbaxy. [00:46:29] Katherine explains why Peter Baker eventually left the FDA despite the good work he was doing. [00:48:18] Dawn mentions that in light of Baker’s and other FDA investigators’ discoveries of fraud and corruption in China and India, stronger regulations are needed in order to protect consumers. She asks if Katherine has a sense of what direction the FDA is headed in that regard. [00:49:39] Ken asks if we should start producing more of our own drugs in the U.S. [00:50:30] Katherine explains the resource on her website titled “A Guide to Investigating Your Own Drugs.” [00:52:21] Dawn asks about Valisure, a mail-order pharmacy that tests every drug that they dispense to ensure quality. [00:54:18] Dawn mentions that Katherine was recently in India to do some talks and book signings, but that she had concerns about the reception because the Modi Government had put out a statement saying that it was going to take action against her book. [00:55:39] Ken asks if Katherine is working on any new projects at the moment. [00:56:13] Ken asks if Katherine is still in touch with Harry Lever at the Cleveland Clinic, or “4 Dollar Refill.” [00:56:47] Dawn closes the interview asking about Katherine’s 187-pound dog Romeo.Links:
Episode 103: Abe Morgentaler talks about men’s health, sex drive and the benefits of testosterone therapy
Today’s interview is with Dr. Abraham Morgentaler, an internationally known pioneer in men’s sexuality and the founder of the first comprehensive center in the U.S. specializing in men’s health.
Abe’s research has upended longstanding concepts regarding testosterone therapy, prostrate cancer and male sexuality. He is particularly credited with research that has contradicted the established view that testosterone injections led to elevated risks for prostate cancer.
In today’s interview, we talk to Abe about testosterone deficiency and its effects on men’s health and sex drive; the biological functions of testosterone; and Abe’s work treating metastatic prostrate cancer.
Abe is the director of Men’s Health Boston and an associate clinical professor of Urology at Harvard Medical School. He is the author of “Why Men Fake It: The Totally Unexpected Truth About Men and Sex,” which was retitled “The Truth About Men and Sex” for the paperback edition. He also is the author of “Testosterone for Life: Recharge Your Vitality, Sex Drive, Muscle Mass and Overall Health.”
Show notes
[00:02:58] Dawn opens the interview mentioning that Abe grew up in Canada, asking him what his interests were as a kid other than hockey. [00:04:28] Dawn asks what Abe’s gap year between high school and college was like. [00:07:48] Abe explains that when he was born, his mother had some specific wishes for him. He failed at one but came through on the other. [00:08:17] While a sophomore in college trying to find his way, Abe ended up studying sex hormones in lizards. [00:16:32] Dawn explains that for a long time the greatest fear related to the use of testosterone therapy was that it would lead to prostate cancer. This was based on a 1941 paper by Charles Huggins from the University of Chicago, who wrote that his research found cancers were sensitive to hormonal manipulation. Dawn asks Abe to discuss how he started questioning this long-held dogma that high testosterone levels caused prostate cancer. [00:23:29] Dawn mentions that this story is a great example of why it is important in science to question things, particularly the status quo. [00:31:50] Abe talks about his 2006 paper, “Testosterone and Prostate Cancer, a Historical Myth,” which showed that the data contradicted the old belief that more testosterone would lead to more prostate growth. [00:40:10] Ken mentions that Abe followed up his previously mentioned paper with another one titled, “The Saturation Model and the Limits of Androgen-Dependent Growth.” [00:45:19] Abe talks about the exciting work he is doing helping men deal with metastatic prostate cancer. [00:51:32] Dawn explains how Abe uses the term “low T” to describe a condition that is otherwise known as hypogonadism or testosterone deficiency syndrome. Abe describes the many biological functions of testosterone. [00:53:27] Abe responds to the criticism that because testosterone levels decline with age, the process must be natural and, therefore, should not be treated. [00:55:42] Abe discusses a paper that came out in 2013 in the Journal of the American Medical Association that reported increased cardiovascular risk in men given testosterone replacement, and how the study’s statistical analysis was seriously flawed. [01:07:03] Ken mentions that in 2017, a trial by Budoff et al., published in JAMA, suggested that testosterone replacement therapy in men with low T led to more rapid progression of atherosclerotic plaques compared to placebo. [01:13:21] Ken asks why Abe thinks that testosterone replacement therapy can actually be protective in regards to cardiovascular disease. [01:14:19] Ken asks about the seemingly rapid drop in testosterone levels in men in the western world as reported by several papers including the Massachusetts Male Aging Study, as well as a large Finnish Study, and a 2017 meta-analysis. [01:17:37] Dawn mentions that while most people are aware of the term menopause, most are less familiar with the term andropause, coined as the male equivalent. [01:20:41] Abe explains why blood tests for low T can be deceiving, and alternative tests that produce more practical results. [01:25:55] Dawn asks about Men’s Health Boston, which Abe founded in 1999, which was the first comprehensive men’s health center in the United States. [01:29:18] Ken asks about the different modes and types of testosterone administration. [01:33:21] Ken asks about the fears of the aromatization of testosterone to estrogen with replacement therapy. [01:36:14] Ken asks if there are any studies looking into “super physiological” levels of testosterone, such as levels up to 2000. [01:39:22] Ken mentions that in Abe’s book “The Truth About Men and Sex,” Abe explains that his attempt was to pull back the curtain to reveal men as they truly are, the last chapter being titled, “Men Are People, Too.” [01:43:19] Dawn asks Abe what he likes to do in his spare time. [01:45:36] Dawn mentions that Abe was 18 when he entered Harvard as a freshman, and asks him if he had any idea that he would still be at Harvard more than four decades later.Episode 102: Adam Konopka talks about metformin’s effects on healthspan and lifespan
Our guest today is Dr. Adam Konopka, an assistant professor in the Department of Kinesiology and Community Health at the University of Illinois Urbana Champaign, who believes that aging is the greatest risk factor for just about every single chronic disease that exists.
Adam’s lab, called the Musculoskeletal Aging and Metabolism Lab, is focused on aging-related research.
In addition to doing research that looks at different ways to delay the onset of age-related diseases and functional decline, Adam also has done a lot of research related to the interaction of exercise with metformin. Adam and his colleagues had a paper in Aging Cell that suggested metformin may blunt the health benefits of exercise in healthy older adults, a study that attracted a lot of attention and was highlighted in a story in The New York Times back in June.
Show notes:
[00:03:59] Dawn opens the interview mentioning that Adam’s lab is at the University of Illinois, and asks if he decided on Illinois because he grew up in a suburb outside of Chicago. [00:04:28] Dawn asks Adam how he ended up getting into competitive swimming. [00:05:13] Adam explains how his involvement in swimming increased his curiosity about physiology and ways to improve performance, a line of thought that contributed to his eventual majoring in exercise science. [00:05:49] Dawn asks Adam why he decided to minor in entrepreneurship. [00:06:18] Dawn asks Adam about the time when a professor doing research in pediatrics gave Adam the opportunity to volunteer for a study. [00:07:01] Ken mentions that while Adam was a student, he had the opportunity to work on a study which looked at an exercise program used by crew members aboard the International Space Station. Adam explains what his role in this study was. [00:08:05] Adam talks about his time spent at the Mayo Clinic as a postdoctoral research fellow, where he focused his time on looking at skeletal muscle mitochondrial function. [00:09:00] Dawn explains Adam’s notion that mitochondria contribute to obesity induced insulin resistance, a highly debated topic. Dawn goes on to mention Adam’s 2015 paper that looked at obese women who had defects in mitochondrial efficiency and hydrogen peroxide emissions. Adam explains how exercise effectively restored the mitochondrial physiology of these women to that of a leaner phenotype. [00:10:36] Adam discusses a metformin study he was a part of while at the Mayo Clinic, where he tested a hypothesis that had been previously shown in cell culture, to learn if those findings were translatable to humans. [00:11:51] Adam talks about the significance of his findings that metformin improved fasting and postprandial glycemia without inhibiting glucagon-stimulated glucose production. [00:12:59] Ken asks about the two and a half years Adam spent at Colorado State and the research that he conducted there. [00:13:32] Adam explains the mission of, and the research being done at, his lab, The Musculoskeletal Aging and Metabolism Lab, at the University of Illinois. [00:16:25] Ken asks Adam if he has looked into rapamycin and muscle, with respect to mTOR inhibition. [00:17:01] Dawn mentions that Adam took these earlier studies, as well as the research he did as a postdoc, and started asking questions related to the interaction of exercise with metformin. [00:17:30] Ken mentions how this research led to Adam’s paper earlier this year, which was highlighted in the New York Times, and which cast doubt on the idea that exercise and metformin, both of which have been looked at in the context of healthspan extension, work well together in conjunction. [00:19:24] Dawn asks if the negative effects of metformin documented in various studies are relatively modest and or negligible. [00:20:30] Ken asks Adam to speculate on some of his findings, particularly why a certain portion of individuals dosed with metformin are likely to be negative-responders, but at the same time others are positive-responders. Adam talks on this wide variability in the response to metformin. [00:23:12] Dawn asks about Adam’s follow-up research into exercise and metformin that he received a grant for. [00:25:20] Ken mentions it has been suggested that people space out the taking of metformin from the time a person exercises, given that the half-life of metformin is six hours. [00:27:03] Dawn asks if the widely reported health benefits of metformin are worth it possibly inhibiting beneficial mitochondrial adaptations to exercise in older adults. [00:28:38] Dawn asks for Adam to speculate on the mechanisms behind how metformin blunts the adaptive response to exercise. [00:30:48] Ken talks in regards to the NIH-funded trial into metformin called, “Targeting Aging with Metformin” or TAME. Ken asks about Adam’s paper in GeroScience titled, “Taming Expectations of Metformin as a Treatment to Extend Healthspan.” [00:32:57] Ken mentions that he would have liked to have seen rapamycin used instead of metformin in the TAME trial. [00:33:42] Dawn asks if Adam believes that a metformin trial in healthy individuals is currently warranted. [00:34:38] Dawn mentions that while metformin undoubtedly helps individuals suffering from metabolic disease, it is unclear if it has any significant positive effects on already healthy individuals. She goes on to mention that this is paradoxical in light of the fact that the majority of popular interest in off-label use of metformin is in healthy individuals or the so called “worried well,” people who already follow habits of good health. [00:36:16] Ken asks Adam how, in a perfect world, he would design a trial for healthspan-extending intervention in regards to what intervention would he pick, and how he would gauge efficacy considering that an intervention in healthy individuals would ideally need to be continued for several decades in order to determine a true effect. Ken goes on to ask what the pros and cons are of proxies for age in such a study including telomere length as well as biological and epigenetic clocks. [00:39:26] Ken asks how Adam would adjust for lifestyle behaviors like dietary manipulation and exercise that activate similar pathways to drugs like metformin and rapamycin in his hypothetical study. [00:40:44] Dawn asks if Adam has much expectation in extending lifespan with pharmacological methods, or if he thinks that merely healthspan will increase while we see a so-called compression of morbidity, and if he thinks that these pharmacological treatments are likely to surpass lifestyle interventions like exercise. [00:42:39] Ken asks if Adam has looked at PPAR-D agonists, which are a class of drugs that provide some of the effects of exercise pharmacologically. [00:43:50] Adam gives his advice to people interested in extending their healthspan. [00:44:57] Dawn asks what Adam’s diet and exercise routine look like. [00:46:11] Dawn mentions that she knows that Adam and his wife have a young child and closes the interview asking Adam what he does for fun in his spare time.Links:
Musculoskeletal Aging and Metabolism Lab Facebook page
Episode 101: Rachel Yehuda talks about epigenetic inheritance, PTSD and the potential of MDMA therapies
Today we talk with Dr. Rachel Yehuda whose pioneering research on cortisol and brain function has revolutionized worldwide our understanding and treatment of post-traumatic stress disorder.
Rachel is also well-known for her studies on the intergenerational transmission of trauma and PTSD. This novel research has shown that the children of traumatized parents are at risk of similar problems due to epigenetic changes that are transmitted from the parents to their offspring. She has worked with war veterans, Holocaust survivors and other victims of trauma to detail the biological roots of PTSD.
She is a professor of psychiatry and neuroscience and the director of the Traumatic Stress Studies Division at the Mount Sinai School of Medicine in New York City. She also is the director of the Mental Health Patient Care Center at the James J. Peters VA Medical Center.
Show notes:
[00:02:31] Dawn begins the interview asking Rachel about her time as a child growing up in Cleveland. [00:03:17] After Ken mentions that Rachel’s father was a rabbi, Rachel explains how growing up in an observant Jewish household shaped her. [00:04:46] Rachel talks about a biology teacher who inspired her to go beyond her interests in philosophy and pursue science. [00:05:50] Dawn asks Rachel why it seems that so many scientists start out with an interest in philosophy. [00:07:16] Dawn asks Rachel why she decided to major in psychology at Touro University in New York. [00:08:16] Ken asks Rachel why she decided to attend the University of Massachusetts at Amherst after graduating from Touro University. [00:09:03] Rachel explains how she went into graduate school looking for a way to become both a psychologist and a scientist. [00:10:08] Dawn asks Rachel about something Rachel’s daughter observed about her: “You move to the beat of your own drum. You never do anything other than what the voice in your head tells you to do.” [00:11:12] Ken asks if it is true that Rachel’s first graduate advisor was not optimistic about Rachel making it through grad school. [00:12:33] Rachel tells the story of how she first met Bill Edell and walked up to him and said that she wanted to do clinical research. [00:14:38] Ken asks Rachel why she decided to do research on stress, particularly when stress wasn’t a major focus of research in the 1980s. [00:16:05] Dawn mentions that after graduating from UMass Amherst, Rachel did her postdoctoral work in biological psychiatry at Yale Medical School. Rachel met Dr. Earl Giller there, who became Rachel’s mentor and an early researcher in post-traumatic stress disorder. Rachel talks about how Dr. Giller had just completed a study on Vietnam veterans showing low cortisol levels. [00:18:40] Rachel talks about how for her post-doc at Yale she wanted to look into the biology of personality, but was told that it was a “dumb idea” for post-doc research. [00:22:06] Dawn asks about the paradox uncovered by Dr. Giller’s research into Vietnam veterans showing low cortisol levels when stress is supposed to be associated with elevated cortisol levels. Dawn goes on to ask how this finding led Rachel to interview Holocaust survivors in her hometown of Cleveland. [00:24:43] Rachel tells the story of when she talked to a group of Holocaust survivors, a woman came up to her and said: You know, Dr. Yehuda, we don’t have VA centers like your veterans do. [00:26:20] Ken asks about the program Rachel set up to help Holocaust survivors. [00:27:20] Dawn points out that in 2016 Rachel published the results of a study looking at the genes of 32 Jewish women and men. She and her colleagues at Mount Sinai studied Holocaust survivors who either had been interned in Nazi concentration camps during World War II or had witnessed or experienced torture. Rachel also looked at the genes of 22 children who were born to the Holocaust survivors after the war. Rachel discusses how the changes in the DNA of Holocaust survivors were in a way passed down to their offspring. [00:29:13] Rachel discusses the necessary caution we should take regarding our understanding of mechanisms and how effects get from one place to another, or from the experience of one generation into the biology of the next, because we simply don’t have sufficient human studies that can truly pinpoint what truly causes the effects we see. [00:32:06] Ken asks about Rachel’s realization that past effects could transform not only the narrative of a person’s life but also their physiology. [00:33:59] Dawn describes Rachel’s 2005 study with woman who were pregnant in the World Trade Center during 9/11, which showed, along with other studies, that children of traumatized parents are at risk of having similar problems as their parents due to changes occurring in the biology of the parents as a result of trauma exposure. Dawns asks about the process of epigenetic changes being transmitted to offspring, which has become known as “intergenerational transmission.” [00:36:27] Ken asks if cortisol is uniformly low, or if there is substantial variation from person to person, since one often hears of elevated cortisol levels in first responders and military populations. [00:38:43] Ken asks Rachel how she ended up at Icahn School of Medicine at Mount Sinai. [00:39:40] Ken asks about Rachel’s role as the founder and director of the Division of Traumatic Stress Studies at Mount Sinai. [00:41:20] Dawn asks Rachel to describe what happens inside a person’s body when they find themselves in a stressful situation. [00:42:47] Dawn mentions that in psychiatry and mental health, symptoms of trauma are treated as psychological, but that Rachel is finding that these problems of trauma also correlate to people having physical problems. [00:44:02] Rachel talks about her role as the Director of the Mental Health Patient Care Center at James J. Peters Veterans Affairs Medical Center in the Bronx, which she has inhabited since 2009. [00:44:58] Rachel is asked to talk about how there are only a few approved pharmacological treatments for PTSD, and no approved medications to enhance resilience. [00:46:38] Ken asks about a study Rachel published in 2013 which indicated that effective psychotherapy can be thought of as a form of “environmental regulation” which is able alter a person’s epigenetic state. [00:49:36] Ken asks how Rachel thinks the discovery of the epigenetic inheritance of trauma could change the way we approach and treat chronic health conditions, and if it is possible that much of what we are experiencing in terms of physical and mental illness as a society at large could be manifestations of trauma that has been caused by changes to epigenetic memory. [00:51:09] Rachel describes her excitement about MDMA-assisted psychotherapy for PTSD, an interest she is collaborating on with Dr. Dave Rabin, who was interviewed on STEM-Talk episode 99. [00:52:14] Dawn refers the MDMA study that Rachel and others are collaborating on with Dave, and how this study has started its phase III trial with the FDA. Rachel gives an overview of what is going on with this study and how MDMA could be licensed and become a medicine. [00:56:09] Ken asks Rachel about her quote where she said in an interview, “My career has been enhanced by the fact that early on nobody believed in PTSD. Well, now, I almost think we’ve been a victim of our own success in many ways because I think we’ve ended up really pathologizing it to a large extent.” [00:58:37] Ken comments on how he relates to Rachel, in that his early career saw him also studying something believed to be impossible, AI, and that things have now been reversed and the power of AI is often overestimated. [00:59:45] Rachel explains that she is thankful to have become a scientist, even though she enjoyed philosophy in her youth, but that if she could no longer be a scientist for some reason, she would want to become a musician. [01:00:15] “Dawn mentions that Rachel has some experience appearing on stage as a singer, such as when she performed at the Meeting of the International Society of Psychoneuroendocrinology with colleagues Thomas Neylan and David Spiegel (interviewed on STEM-Talk episode 45). The song Rachel sang was titled “The Grant Song,” Dawn closes the interview asking Rachel if she wrote the humorous lyrics.
Episode 100: Peter Attia gives an update on his views regarding longevity and health span
Today’s episode marks the 100th episode of STEM-Talk and the return of guest Peter Attia, who Ken and Dawn interviewed for episode one of STEM-Talk back in 2016.
Peter is the founder of Attia Medical, a medical practice with offices in San Diego and New York City that focuses on the applied science of longevity. Peter emphasizes nutritional biochemistry, exercise physiology, sleep physiology, lipidology, pharmacology and four-system endocrinology to help people increase their lifespan and health span.
Peter is the host of the podcast The Drive. He earned his M.D. from Stanford University and holds a B.S. in mechanical engineering and applied mathematics.
Show notes:
[00:04:44] Dawn opens the interview welcoming Peter back to the show. Dawn mentions that a lot has happened since she and Ken last interviewed Peter and points out that Peter is in the process of writing a book. [00:05:51] Ken asks Peter if it’s true that he does his best writing on long flights. [00:06:21] Dawn mentions that in 2014 Peter created Attia Medical, which is a practice with offices in San Diego and New York City, where he focuses on the applied science of longevity and optimal performance. Peter gives an overview of his practice and how he works to improve people’s healthspan and lifespan. [00:07:29] Ken asks Peter to explain the difference between a strategy and a tactic in the domain of optimization of performance and healthspan. [00:10:35] Dawn mentions that back on episode one of STEM-Talk that Peter talked about his eight drivers of longevity. Dawn asks Peter if his thinking over the past three years has changed in terms of the eight drivers. [00:12:30] Dawn asks what are some of the best lab tests in terms of longevity that people should request from their primary care physician. [00:14:25] Ken asks how Peter goes about determining optimal reference ranges to target in his patients, noting that the guidelines constituting normal are based on a sick overall population. [00:17:26] Dawn talks about how every year a new secret to longevity comes out with the force of hype behind it, but that rarely does the new so-called secret deliver. In contrast, she mentions how Peter encourages people to keep things simple and focus on nutrition, exercise and sleep. Peter explains how these three things can have the biggest impact on a person’s physical health. [00:19:35] Dawn explains that optimizing health span can be expensive, often costing upwards of $100,000 a year in tests and devices and off-label medications. She asks if Peter has any thoughts on if there is becoming a class divide in the world of healthspan and lifespan. [00:21:10] Ken explains that a primary inhibitor of BDNF is HDAC, and BHB is a powerful inhibitor of HDAC, which leads one to think that one of the mechanisms of exercise to increase BDNF is the elevation of BHB. [00:22:21] Ken mentions that the area under the curve for insulin is one of Peter’s favorite longevity markers, and asks him to talk about the concept of insulin area under the curve. In addition to blood tests and glucose monitoring, Ken asks Peter what would be the next item of greatest interest in terms of longevity markers. [00:24:28] Dawn mentions that Peter wears an Oura Ring to monitor his sleep, and a glucose monitor to measure his blood sugar in real time. Dawn asks Peter to talk about the benefits of continuous monitoring versus short-term use for the purpose of building future behavior. [00:25:54] Dawn asks if Peter uses any other wearables besides the ones she just mentioned. [00:27:45] Dawn points out that Peter traveled to Easter Island with some friends, including David Sabatini, a guest on episode 70 of STEM-Talk. Dawn asks Peter to talk about the trip which was set up to explore first-hand the place where a group of Canadian researchers first discovered rapamycin. [00:29:13] Ken mentions that Peter is on record saying, “For me personally nothing is more interesting than rapamycin.” Peter explains what he has been learning about rapamycin and why it is so fascinating. [00:31:49] Ken says that in one of Peter’s podcasts, Peter mentioned he had been taking 5 mg of rapamycin. Ken asks what it was that informed that choice. Ken also asks Peter how he has been tracking rapamycin’s effects, and if he has any thoughts for listeners considering rapamycin. [00:33:38] Dawn asks if we are any closer to being able to accurately measure biological signals, such as mTOR activity and autophagy, than we were three years ago. [00:36:28] Peter explains his thoughts on muscle loss and fasting, and the amino acids that are important in muscles affected during a fast. [00:38:44] Ken mentions that there are a lot of misconceptions about protein consumption, particularly in the context of ketogenic diets. He mentions Valter Longo’s opinion that a diet high in protein is as bad as smoking. Peter explains his thoughts on the role of protein in health and performance. [00:41:05] Ken makes the point that the strongest viewpoints in science that have the most passion and anger behind them are often the ones with the largest error bars. [00:41:35] Dawn mentions the importance of IGF-1 and its related molecules on metabolism. She asks about the paradox when it comes to IGF-1 in terms of performance and longevity. [00:43:39] Ken mentions that the Annals of Internal Medicine published a study that made the point that eating red meat poses minimal health risks. Peter gives his thoughts on this. [00:48:39] Ken states that in addition to rapamycin and fasting, he and Peter share an interest in sauna, a practice with growing evidence for its benefits. Ken asks Peter’s opinion on the difference between infrared and traditional sauna. [00:50:03] Dawn mentions that in 2016 the Dong et al paper in Nature suggested that the limit of human longevity has been reached, and that Barbi et all published a paper in Science in 2018 that said that the mortality curve for humans flattens out once the age of 105 is reached. Peter shares his thoughts on just how long humans can live. [00:53:29] Ken mentions that a recent study from the Miller Lab suggested that metformin might inhibit mitochondrial adaptation in older adults, and that an even more recent paper out of the University of Kentucky and the University of Alabama reported that metformin significantly blunts muscle hypertrophy in response to resistance training. Peter gives his thoughts on this and why he stopped taking metformin. [00:55:36] Peter shares his concerns about generic metformin, as well as his recent interview with Katherine Eban about the fraud in the generic drug industry. [00:57:15] Ken mentions that Peter is a proponent of fasting, and is involved with the Zero app. Ken asks if the benefits of fasting can be thought of in relationship to ApoB levels. [00:59:18] Ken asks Peter to describe what he sees as the most interesting question he doesn’t yet have an answer to, but believes is eventually possible to know. [01:00:28] Dawn ends the interview by asking Peter if there is one thing that he did not believe three years ago that he now thinks is likely to be true.Links:
Episode 99 : Dave Rabin on how psychedelics and wearable devices can help improve people’s lives
Dr. David Rabin is the chief innovation officer and co-founder of Apollo Neuroscience. He also is the co-inventor of Apollo, a wearable device designed to improve focus, sleep and access to meditative states by gently delivering layered vibrations to the skin.
Dave is a board-certified psychiatrist and translational neuroscientist who for the past decade has been studying resilience and the impact of chronic stress on humans. He received his MD in medicine and Ph.D. in neuroscience from Albany Medical College in Albany, New York. He trained in psychiatry at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center.
Dave also has organized the world’s largest controlled study of psychedelic medicines and is well-known for his research into MDMA and its potential to treat post-traumatic stress disorder along with other disorders.
Show notes
[00:03:06] Dawn opens the interview mentioning that David grew up in California and asking him about an insatiable need he had as a child to understand why people were the way that they were. [00:04:18] David talks about how the vivid and frequent dreams he had as a child played a role in his decision to study consciousness and neuroscience. [00:07:33] Dawn mentions that in high school Dave told his father that he wanted to study consciousness; however, Dave’s father suggested that he study something more tangible and quantifiable instead. Dave explains how this led him to spend the summer between his junior and senior year of high school at Rockefeller University. [00:12:08] Ken asks why Dave decided to move across the country to Albany Medical College, where he received his MD in medicine and Ph.D. in Neuroscience. [00:14:01] Dave gives an overview of the research he did, while working on his Ph.D., in emotional salience and how people interpret different stimuli as either threatening or safe. An area of research informed by his reading of evolutionary psychology, and the study of touch as an evolutionarily conserved stimulator of the safety pathway. [00:17:58] Ken asks about how Dave decided to go into psychiatry at Western Psychiatric Institute and Clinic at the University of Pittsburg Medical Center, where he focused on treatment-resistant mental illnesses. [00:20:47] Dawn mentions Dave’s work with Greg Siegel. Dawn asks about this work and how it led Dave to become serious about studying consciousness, altered states of consciousness, and the potential use of these altered states to facilitate healing. [00:24:26] Ken talks about MDMA, or 3,4-Methylenedioxymethamphetamine, a psychoactive drug commonly known as ecstasy or molly. He explains that MDMA has been shown to facilitate the release of oxytocin, which increases levels of empathy and closeness while dampening fear-related amygdala activity. This results in an overall decrease in stress response and social anxiety. Ken asks Dave to talk about MDMA’s potential to treat PTSD (posttraumatic stress disorder) along with other disorders. [00:27:37] Ken asks if Dave has seen any improvements in heart rate variability (HRV) post MDMA treatments. [00:28:37] Dawn mentions that Dave is part of the world’s largest controlled study of psychedelic medicines. She goes on to explain that these medicines, like LSD and MDMA and even psilocybin, which comes from mushrooms, were used to treat mental and emotional trauma from the 1950s to the ‘70s. Due to the abuses that occurred during this time, the use as well as research on psychedelic medicines in U.S. were shut down. With a shift towards a renewed interest in these medicines, Dawn asks about this study and if Dave could give a background on psychedelic medicine. [00:32:34] Dave talks about the epigenetic trial, being conducted in phase three of the MDMA study, where DNA samples are collected before and after use, to determine the epigenetic regulation of stress-response genes. [00:41:30] Ken asks about psilocybin, which is a naturally occurring psychedelic produced by more than 200 species of mushrooms. Ken asks Dave to explain how psilocybin is different from MDMA, both chemically and experientially. [00:45:45] Dave discusses the use of ecstasy and the debate around the safety of MDMA, and how compared to stimulants such as cocaine, amphetamine and methamphetamine, addiction to MDMA is very rare. [00:48:47] Dawn explains that psychedelics are, to this day, illegal in the U.S., and further states that STEM-Talk is not advocating the use of these or any illegal substances, before asking Dave about the changing legal status of psychedelics. [00:49:51] Dawn asks about the use of cannabidiol (CBD) for management of symptoms for illnesses such as PTSD and pain-management. [00:54:17] Ken mentions that Dave has spent the last several years developing a technology called Apollo, which is intended to help people make changes more effectively. Given the research and study Dave has done into stress, meditation and athletic performance, and why some people are more resilient than others, Ken asks Dave what he has learned from all this and how it led to the Apollo technology. [00:57:31] Ken asks if the hypervigilance people have to text alerts and emails and phone vibrations and news alerts and the constant bombardment of noise and stimuli is conditioning our bodies to be in a hyper-stressed state all the time. [00:59:26] Ken asks how to retrain the nervous system to become more balanced between our sympathetic and parasympathetic symptoms without the use of psychedelics. [01:02:37] Dawn asks about cognitive patterns and the way people think about their lives, such as the tendency to take challenges personally and think “why me?” while others tend to see challenges as an opportunity for growth. [01:05:35] Dave talks about heart-rate variability (HRV) and why he considers it one of the more important findings about resilience that has been made in the past 15 years. [01:09:19] Dawn asks what a good range for HRV is, or if there is a significant degree of variation across healthy people. [01:10:31] Dave explains the Apollo wearable device in depth, and how and why it works. [01:11:57] Ken asks if there have been pilot studies with children for the Apollo device. [01:14:14] Dawn mentions that Dave’s wife Kathryn was the one who came up with the idea to create the company Apollo Neuroscience. Dave tells the story behind that. [01:15:37] Ken mentions that David and Kathryn are in in the process of launching Apollo, and that the devices will start shipping in January. [01:15:50] Dawn asks, given Dave’s study of stress and the pervasiveness of technology in our modern world and its role in our levels of stress, how he deals with stress on a day-to-day basis. [01:18:12] Dawn mentions that Dave went to work for his wife this last year and asks, aside from their working relationship, what the two of them do for fun.Links:
Episode 98: Steven Austad talks about aging and preserving human health
Our guest today is Dr. Steven Austad who studies virtually every aspect of aging. He is a distinguished professor and chair of the Department of Biology at the University of Alabama, Birmingham.
In addition to being recognized for his aging and longevity research, Steve is also well-known for his background as a New York City cab driver, newspaper reporter and a lion trainer who then decided to become a biologist.
His research today involves developing lifestyle and pharmacological approaches to improving and preserving human health. He is particularly focused on figuring out why different species age at different rates.
Steve is the author of more than 190 scientific articles. His book, “Why We Age: What Science Is Discovering about the Body’s Journey Through Life,” has been translated into nine languages. He also writes newspaper columns and has written for publications like Natural History magazine, Scientific American and International Wildlife.
Show notes:
[00:02:53] Dawn opens the interview mentioning that Steve was born in Southern California, but that his family moved around so much, that he ended up attending around 20 grade schools. Steve explains that his father bought a travel trailer and moved the family around the country. [00:03:57] Steve talks about how even though he was shy and introverted as a kid, he found a way to fit in with his classmates. [00:04:40] Ken mentions how Steve’s career went through several reinventions before settling into a career in science. Among the various occupations Steve had were: a newspaper reporter, training lions and tigers for television and movies, and taxi driving. Ken asks Steve how he became a taxi driver. [00:06:01] Steve talks about his time on the West Coast in Portland working as a newspaper reporter for the Oregonian. [00:07:48] Dawn asks how it was that Tippi Hedren and Melanie Griffith had something to do with Steve becoming a lion trainer. [00:14:39] Ken asks Steve about the suicidal duck whose reckless abandonment nearly resulted in Steve’s death at the hands of one of the lions he was training. [00:19:21] Steve discusses why his fascination with animal behavior lead him to California State University to major in biology. [00:23:24] Dawn asks what took Steve to the University of New Mexico for his postdoc. [00:28:16] Ken asks how Steve landed his job as assistant professor in the Department of Organismic and Evolutionary Biology at Harvard University in 1986. [00:29:59] Dawn mentions that Steve discovered that opossums of the predator-free barrier island of Sapelo Island lived 25 percent longer than their cousins on the mainland of Georgia. Steve discusses this and explains how this discovery played a role in his future research. [00:34:13] Dawn points out that Steve left Harvard for the University of Idaho where he became a full professor and then next went the University of Texas. Dawn asks Steve about accepting a position in 2014 at the University of Alabama, Birmingham. [00:41:32] Steve discusses his research into lifespan and healthspan and longevity and why some species age at different rates, with a particular interest in long-lived organisms like quahogs clams and hydra. He goes on to explain how this research led to what he refers to as the “Longevity Quotient.” [00:48:42] Ken mentions that as a former Rhode Islander, he spent some time digging Quahogs and eating them. [00:53:14] Steve gives an overview of how dietary restriction studies are performed on mice. [00:59:39] Ken mentions that from Steve’s description it seems that modern humans are becoming more and more like laboratory mice. [01:02:53] Ken mentions STEM-Talk episode 79 where Satchin Panda talks about time-restricted eating, and episode 7 where Mark Matson talks about intermittent fasting. Ken goes on to say that Mark made the point that the benefits of time-restricted eating or intermittent fasting is that it puts the organism, particularly the human, in a state of ketosis. [01:04:09] Steve talks about the differences in the maximum lifespans of males and females in both humans and other animals. [01:08:42] Ken recommends STEM-Talk episode 67 with Doug Wallace for listeners interested in hearing more about mitochondria. [01:09:44] Dawn asks about metformin, which is a drug that many people believe has the potential to increase our healthspan and lifespan. She asks why it is that we’re not all taking metformin and if it really has such potential. She further asks about the status of the Targeting Aging With Metformin (TAME) trial. [01:13:39] Ken mentions a recent study coming from the Miller lab, that suggested metformin might inhibit mitochondrial adaptations to exercise in older adults. He goes on to mention an even more recent paper out of the University of Kentucky and the University of Alabama, Birmingham has reported that metformin blunts muscle hypertrophy in response to resistance exercise training in older adults. Ken also mentions Steve’s continued interest in rapamycin and its effect on the health span of animals. Ken asks what Steve has learned and if rapamycin would still be his first choice for testing for a drug to target aging. [01:20:08] Ken asks about the optimal and most efficacious dose of rapamycin for humans. [01:21:10] Dawn mentions a paper Steve co-authored with Tuck Finch, discussing the role of the different APOE isoforms. Dawn asks about the ancestral isoform and why we see different isoform distributions today compared to hundreds of thousands of years ago. [01:24:59] Dawna asks why we see different isoform distributions between different populations around the globe. [01:26:29] Dawn asks how much of a role lifestyle versus genetics plays in healthspan and lifespan. [01:28:58] Steve talks about of Fauja Singh, who is 108 and didn’t start distance running until he was in his 80s, and who ran a marathon when he was 101. [01:32:17] Ken asks if Steve is still as confident as he was in 2016 when he made a bet with Olshansky over whether there will be one or more 150-year-old human by the year 2150. [01:34:15] Ken asks why we haven’t seen someone exceed Jeanne Calment’s record age of 122 years that she reached in 1997. [01:36:04] Dawn mentions that Steve continues to write articles and columns for newspapers as well as other news outlets. In addition to this Steve also has a website called, “Let’s Talk Science?” where an assortment of his newspaper columns and other writings can be found. [01:37:47] Dawn closes the interview suggesting that Steve might want to explore writing a novel about a young newspaper reporter who ends up driving a Mercedes across California with a lion in the backseat, who then finds himself in a Hollywood mansion living with Tippi Hedrin and Melanie Griffin and watching over the lions and cheetahs that run through the house. Dawn suggests that has the makings of a good book.Links:
Austad’s University of Alabama, Birmingham bio
Episode 97: Francesca Rossi talks about AI ethics and the development of new AI systems
Our guest today is Francesca Rossi, who for the past three years has been an AI Ethics Global Leader at IBM Research as well as an IBM Distinguished Research Staff Member. Prior to her time at IBM, she was a professor of computer science at the University of Padova, Italy.
Francesca’s AI research interests include constraint reasoning, preferences, multi-agent systems, computational social choice, and collective decision making. Much of her research today is focused on the future of artificial intelligence and the ethical issues surrounding the development and behavior of AI systems.
She is a fellow of both the worldwide association of AI (AAAI) and of the European Association of AI. She also has been president of the International Joint Conference on AI and the editor in chief of the Journal of AI Research.
Sitting in for Dawn during today’s interview is IHMC colleague Brent Venable, who recently was named the inaugural director of a new Ph.D. program in Intelligent Systems and Robotics that is a partnership between IHMC and the University of West Florida.
Brent is a graduate of the University of Padova and had Francesca as her academic advisor.
Show notes:
[00:03:25] Brent opens the interview asking Francesca where she grew up in Italy. [00:03:51] Brent mentions that Francesca was a curious child, who was fascinated with the moon landing. Brent asks what else Francesca was interested in as a child. [00:05:01] Francesca explains that if she were to stumble across a time machine she would be interested in going forward in time rather than backwards. [00:05:41] Ken asks why Francesca decided to study computer science in 1981when the field was relatively new. [00:07:22] Francesca discusses the one class in her academic career that stumped her, despite her good grades in every other subject. [00:08:36] Ken mentions that Francesca ended up in Austin, Texas after obtaining her degree in computer science, and asks what it was that lead her to the University of Texas and what research she did there. [00:11:40] Brent asks why Francesca decided to go back to Pisa after Texas to work on her Ph.D. [00:13:23] Brent mentions that after Francesca’s Ph.D., she moved to the University of Padova, where she worked for the next 20 years. Brent asks about the work that Francesca did in this period, particularly her seminal work on preferences for intelligent systems. [00:15:17] Ken discusses how Francesca became Brent’s academic advisor at Padova. Ken mentions that he has heard that the two of them had so much fun working together, that they did as much laughing as research during their time at Padova. He asks the two of them if that could possibly be true. [00:17:41] Francesca talks about the sabbatical she took to the Radcliff Institute. [00:22:00] Brent asks about an article in the Wall Street Journal that featured Francesca as well as a senior manager at IBM and one of the founders of Skype and how the article played a role in Francesca’s decision to move to the United States. [00:23:41] Francesca’s title at IBM is “Global Ethics Leader.” Brent asks Francesca to describe what the job entails. [00:30:00] Ken asks what Francesca envisions as the likely future of AI, and what she hopes for the future of AI. [00:31:54] Francesca discusses how we sometimes craft our visions for the future around our current technology, and that she believes that the proper approach should be to build our technologies around our visions for the future. [00:34:37] Brent asks Francesca for her thoughts on whether or not the fear of robots and AI going rogue and hurting people is a legitimate one, and what she thinks about the government adopting AI legislation. [00:38:23] Francesca gives her thoughts on the fears that AI will one day replace human workers. [00:41:43] Brent mentions that Matt Johnson, interviewed on episode 86 of STEM-Talk, had an article in AI magazine where he discussed human machine teaming, and said that humans and AI should work together the way two musicians do when playing a duet. [00:44:11] Ken asks about the current predominance of machine learning as opposed to traditional AI, otherwise known as symbolic AI, and if the area of preferences that Francesca has pioneered could be a potential candidate for bringing these two areas of AI together. [00:47:55] Brent asks if we ever decided to one day replace a judge with a deep learning algorithm, would AI be prone to discrimination based on the dataset that the deep-learning algorithm has been given to learn from. [00:52:35] Ken asks if there are ways to hold the people and the companies that design intelligent systems accountable for the decisions that they make? [00:55:29] Ken mentions that tech companies often shift blame to algorithms for mistakes that were a fault of humans whether intentional or unintentional. He asks about the growing concern of biases both consciously and unconsciously being imbedded into algorithms by the humans who make them. [01:00:34] In ascribing values to intelligent machines to abide by, Ken asks whose values should be used, as different cultures have different values as well as different ethical codes of conduct. [01:04:42] Brent asks about Francesca’s involvement with The Future of Life Institute, which leads Francesca to discuss Max Tegmark’s book “Life 3.0.” [01:08:11] Brent asks about another initiative Francesca is involved in called Partnership for AI. [01:10:52] Ken mentions that Francesca is the conference chair for the 34th Annual AAAI Conference on Artificial Intelligence, which will take place in New York City in February. Ken asks what the submissions currently look like and also to talk about the health of the field. [01:13:49] Brent asks what Francesca does with her spare time. [01:15:11] Ken asks Francesca why he was told to reassure her that the STEM-Talk staff would use a photograph of her and not a photograph of “The Terminator” on the STEM-Talk home page next to her episode.Links:
Episode 96: Dick Despommier discusses vertical farming and fly fishing
Today we have part two of our interview with Dr. Dickson Despommier, a microbiologist and ecologist who is the emeritus professor of public and environmental health at Columbia University.
Today’s episode focuses on vertical farming, a concept that Dick and his students came up with in 1999. When Dick’s book “Vertical Farms: Feeding the World in the 21st Century” came out in 2010, there were no vertical farms in the world. Today, there are vertical farms throughout the U.S. and around the globe.
Part one of our interview, episode 95, covered Dick’s nearly 30 years of research into intracellular parasitism and his focus on Trichinella spiralis, one of the world’s largest intracellular parasites.
Dick is the author of five books, including “People, Parasites and Plowshares.” His most recent book, “Waist Deep in Water,” is a memoir of his life-long love of fly fishing, a topic we had so much fun discussing with Dick that we touch on it in today’s episode as well as in part one of our interview with Dick.
Show notes:
[00:02:08] Ken opens part two of our interview with Dick by pointing out that there were no vertical farms in the world when Dick’s book “The Vertical Farm: Feeding the World in the 21stCentury”came out in 2010. Ken asks Dick to give an overview of the idea behind vertical farms and also discuss how the idea gained momentum. [00:06:33} Dick explains how the students’ original concept of rooftop gardens evolved into the idea of growing plants inside buildings. [00:08:14] Dick talks about the growth of vertical farming since 2011 and how Japan is the country that has the highest number of vertical farms. [00:09:26] Ken describes a vertical farm located in the heart of Jackson Hole, Wyo., called Vertical Harvest. It’s a 13,500 square-foot green house that can grow produce that is equivalent to 10 acers of traditional farming. This vertical farm sells produce year-round, mostly to local restaurants and grocery stores, but also to individuals who want to go onsite to buy their produce directly. Ken asks if this is a good example of what Dick was hoping for when he conceived of the idea of a vertical farm. [00:13:16] Ken asks Dick to address the criticisms of vertical farming and how the cost of building these structures outweighs the advantages. [00:17:14] Dawn points out that Dick was named teacher of the year eight times during his time at Columbia and asks him for his thoughts about what it takes to become a good science teacher. [00:19:49] Dawn asks about Dickson’s recently published memoir about his love affair with fly fishing, titled “Waist Deep in Water.” [00:20:39] Dick talks about the literature professor that “Waist Deep” is dedicated to and how the professor inspired Dick to start writing. [00:22:07] Dickson tells the story of how he caught his first trout. [00:29:04] Ken ends the interview by asking about Dick’s favorite Shakespeare quote that Dick says gets to the heart of what really matters in life.Links:
“The Vertical Farm: Feeding the World in the 21stCentury”
https://www.verticalharvestjackson.com/our-mission
“People, Parasites and Plowshares: Learning From Our Body’s Most Terrifying Invaders”
Episode 95: Dickson Despommier talks about 30 years of research into intracellular parasitism
Our guest today is Dr. Dickson Despommier, a microbiologist and ecologist who is the emeritus professor of Public and Environmental Heath at Columbia University. Our conversation with Dick covered a variety of topics and ran so long that we divided his interview into two parts.
Part one covers the nearly 30 years Dick spent conducting research on intracellular parasitism, especially Trichinella spiralis, one of the world’s largest intracellular parasites.
Part two of our interview with Dick focuses on vertical farming. In 1999, Dick and his students came up with the idea of raising crops in tall buildings. When his book, “The Vertical Farm: Feeding the World in the 21stCentury,” came out in 2010, there were no vertical farms in the world. Today, there are commercial vertical farms not only throughout the United States, but also in Korea, Japan, China, England, Scotland, The Netherlands, France, Russia, Dubai, Canada and a host of other countries.
Dick is the author of five books, including “People, Parasites and Plowshares.” His most recent book, “Waist Deep in Water,” is a memoir of his life-long love of fly fishing, a topic we had so much fun discussing that we touch on it in part one and part two of our interview with Dick.
Show notes:
[00:03:40] Ken begins the interview by mentioning that he and Dawn are great fans of two podcasts that Dick helps co-host, “This Week in Parasitism”and “This Week in Virology.” Ken points out that “This Week in Virology” launched in 2008, making Dick an early adapter of science-based podcasting. Ken asks Dick how he got involved in podcasting. [00:06:24] Dawn mentions that Dick was born in New Orleans, and that his parents moved across the country to San Francisco when he was only a year old. Dawn goes on to mention that as a kid Dick liked to play outdoors and collect pollywogs and dragonflies. Dick talks about how his mother encouraged him to bring home spiders and frogs and other specimens he collected on his outdoor adventures. [00:07:14] Ken mentions that when Dick was 11 his family moved again to New Jersey, asking how that came about. [00:09:06] Dawn asks about the beginning of Dick’s lifelong love of fishing that started when he was a child. [00:11:54] After Dick talks about recently spending 20 days in Wyoming, Ken and Dick begin a conversation about their favorite rivers in the state to go fishing. [00:13:57] Ken and Dick talk about their fishing bait of choice when they were kids: Wonder Bread. Ken goes on to ask Dick how his love of fishing also evolved into an interest and fascination with wading into creeks, streams and river beds. [00:14:56] Dick talks about his website “The Living River.” [00:16:39] Dawn asks about Dick’s experience with his high school biology teacher who recognized his curiosity and who played a pivotal role in shaping Dick’s scientific career. [00:20:26] Dawn mentions that Dick almost didn’t go to college, but that he eventually jumped in academics bigtime and earned a bachelor’s degree at Fairleigh, a master’s at Columbia, and his doctorate at Notre Dame. [00:22:29] Dawn asks about Dick’s experience during his postdoc at Rockefeller University where there were 12 Nobel prize winners who would sit down with him and ask questions about his research. [00:23:54] Ken asks Dick about his decision to return to Columbia after his postdoc. [00:27:00] Ken mentions that Dick’s experience at Rockefeller cemented his approach to teaching. Ken asks Dick to talk about how when he returned to Columbia that he became as equally engaged in teaching as he was in research. [00:30:18] Dawn asks Dick about his extensive research into the parasite Trichinella spiralis, something Dick has described as “the worm that would be a virus.” [00:38:09] Dawn asks about Dick’s 1998 article for Parasitology Todayabout the Nurse Cell-Parasite complex of Trichinella spiralis, and how it is unlike anything else in nature. [00:47:19] Ken mentions that Emma Wilson, a researcher who has spent more than 15 years studying Toxoplasma gondii, was the guest on episode 93 of STEM-Talk. Ken asks Dick to discuss what is special about T. gondii. [00:51:28] Ken mentions that just recently researchers at the University of Wisconsin Madison have discovered why cats are the definitive host for Toxoplasma gondii. [00:55:33] Dawn asks about Dickson’s interest and research into ecotones, or the transition area between two biomes, a zone of high disease transmission that leads to the spread of schistosomiasis malaria and a variety of parasitic worms. [01:00:03] Ken asks about the prevalence of hookworm in the South following the Civil War and how eradicating it helped revive the Southern economy. [01:06:47] Ken points out that John D. Rockefeller and others thought they had noticed a certain malaise among many in the American South in the years after the war. Rockefeller put together a commission that was comprised of luminaries across many disciplines who examined possible causes ranging from spiritual to social to psychological to medical. Ken asks Dick to elaborate on this interesting episode and explain how it was connected to Italian tunnel workers? [01:13:56] Ken ends part one of the interview with a humorous story about how he dug through solid rock to build his family’s outhouse in Maine.Links:
“The Vertical Farm: Feeding the World in the 21stCentury”
“People, Parasites and Plowshares: Learning From Our Body’s Most Terrifying Invaders”
Episode 94: John Newman discusses how the ketogenic diet and fasting regulate the genes and pathways that control aging
Our guest today is Dr. John Newman, a geriatrician and researcher who is well-known for a 2017 study that found a ketogenic diet reduced the mid-life mortality of aging mice while also improving their memory and healthspan.
John is an assistant professor at the Buck Institute for Research on Aging and a geriatrician in the Division of Geriatrics at the University of California, San Francisco. He also is a physician who works with older adults in the San Francisco VA Medical Center.
At Buck, John studies the molecular details of how diet and fasting regulate the genes and pathways that control aging. He particularly focuses on the ketone body beta-hydroxybutyrate and how its molecular signaling activities involving epigenetics and inflammation regulate aging and memory in mice.
Show notes:
[00:02:51] Dawn opens the interview asking John what it was like growing up in Long Island. [00:04:20] Dawn mentions that John was described as a pretty geeky kid growing up, and asks him about his childhood. [00:05:40] Ken asks John if being the type of kid who would do all the homework in his textbooks in the first couple of months annoyed his classmates. [00:07:34] Dawn asks why John decided to go to Yale University. [00:08:45] Mentioning that Yale doesn’t have a pre-med program, Dawn asks what John decided to major in. [00:10:15] John explains how he met his wife at Yale. [00:11:28] Dawn asks John why he traveled across the country to the University of Washington after graduating from Yale. [00:12:26] Dawn asks why John decided to focus his graduate work on the progeroid Cockayne syndrome. [00:14:15] John discusses his decision to go to the University of California, San Francisco for his residency. [00:16:05] Dawn asks if John immediately joined the faculty at San Francisco after his residency. [00:17:03] Ken asks John about his work to improve the care of older adults and help them maintain their independence as they age. Ken asks for an overview of the work John and his colleagues do in this area at the Buck Institute [00:18:39] Ken mentions that a lot of John’s work focuses on the molecular details of how diet and fasting regulate the genes and pathways that control aging. Ken asks John to elaborate on this work. [00:20:04] Dawn asks what specifically attracted John to the idea of studying the ketogenic diet as an intervention in mid to later life as opposed to a diet consumed habitually throughout life. [00:23:12] Dawn mentions that John and Eric Verdin, who recruited John to the Buck institute, share an interest in looking at ketone bodies as signaling metabolites, a topic they have written about. [00:26:21] Ken talks about a conference he and Dawn attended on CBD and seizures, where Ken made the point that ketones are a metabolite of THC. [00:27:52] Ken asks John to go into more detail about how ketone bodies may link environmental cues such as diet to the regulation of aging. [00:29:08] Ken talks about how it seems clear that ketone bodies are emerging as crucial regulators of metabolic health and longevity via their ability to regulate HDAC (histone deacetylases) activity and thereby epigenetic gene regulation. He asks John to discuss how beta hydroxybutyrate may be an increasingly useful and important signaling molecule as we age. [00:34:24] Dawn mentions that John and his colleagues published paper in 2017 in Cell Metabolism titled “Ketogenic Diet Reduces Midlife Mortality and Improves Aging in Mice.” Dawn asks why John chose a cyclical rather than continuous ketogenic diet for this study. [00:37:56] Dawn asks why John decided to conduct the test of physiological function while the ketogenic diet group was off the diet, and on a standard high-carbohydrate diet. [00:40:02] Dawn mentions that Megan Roberts and her colleagues at theUniversity of California Davis were also conducting studies on the effects of a ketogenic diet on mice around the same time as John’s study, and that both were published in the same issue of Cell Metabolism. Dawn goes on to mention that Megan was recently interviewed on episode 92 of STEM-Talk where she discussed her paper, “A Ketogenic Diet Extends the Longevity and Healthspan in Adult Mice.” Dawn adds that both Megan’s and John’s studies had similar findings but that Megan’s had the added caveat that the ketogenic diet may also improve strength and coordination. Dawn asks what John’s takeaways were from Megan’s paper and how do the two papers differ? [00:44:50] Ken mentions that he is personally looking at the effect of the ketogenic diet as a way to avoid sarcopenia and other aspects of aging. [00:46:42] John discusses possible reasons why the ketogenic diet has such pleiotropic effects on people suffering from diseases such as type 2 diabetes, epilepsy, inflammation etc. [00:50:17] Dawn mentions that one of the most frequent criticisms of the diet comes from nutritionists who say “show me the five-year data,” she asks how John would respond to that. [00:54:25] Ken asks about the “arctic variant” mutation, and how this mutant might affect ketosis. He asks John to describe the mutation and how he thinks it might be affecting ketone metabolism in the Inuit population, and how the scientific community might go about investigating this further. [01:00:06] Dawn asks if John has used exogenous ketones in his studies. [01:02:21] Dawn asks what the right overlap between the ketogenic diet and exogenous ketones is, and if exogenous ketones might be synergistic with the ketogenic diet. [01:04:17] Ken asks if there is a threshold or target blood level of ketones for people on the ketogenic diet and using exogenous ketones. [01:07:27] Ken mentions that another metabolite that has been shown to affect life span is alpha-ketoglutaric. Ken asks John to speculate as to if the mechanism of life span extension seen here is similar to BHB and if the two might be synergistic. [01:09:30] Dawn mentions that in addition to his work as a researcher at the Buck institute, John is also a geriatrician who cares for older adults who have been hospitalized at the San Francisco VA Medical Center. Dawn asks what sort of work John does with older individuals. [01:11:25] John discusses his perspective on the education and training of future geroscientists. [01:15:01] Dawn asks what the most promising interventions being investigated in geroscience are right now. [01:23:05] Dawn comments that John has been in the Bay area for more than 10 years, going on to ask if it is true that his main interests outside of work are volleyball baseball and food. [01:24:46] Ken ends the interview mentioning that a little birdie told him that John is a connoisseur of the San Francisco pastry-shop scene.Links:
John Newman ResearchGate profile
Episode 93: Emma Wilson talks about Toxoplasma gondii infection and its consequences
Our guest today is Dr. Emma Wilson, a researcher who has spent the past 15 years studying Toxoplasma gondii, a protozoan parasite that infects about a third of the world’s population.
She is a native of Scotland and a professor of biomedical science at the University of California, Riverside.
Toxoplasma gondii is a single-celled organism found in all mammals. The primary focus of Emma’s research is the immune response in the brain following Toxoplasma gondii infection. Her 2016 research paper in the online journal PLOS Pathogens connected the Toxoplasma gondii to brain dysfunction.
Show notes:
[00:03:05] Emma begins the interview taking about growing up was born in Glasgow with parents who were in the acting business. [00:03:38] Emma shares how her father advised her to keep all of her doors open, which lead her as a youth to pursue everything she found interesting. [00:04:30] Dawn asks if Emma decided to major in ecology in an effort to help save the rainforests. [00:05:28] Ken asks about Emma’s experience with a “proverbial crazy professor” who showed her a room full of rattlesnakes and how that experience led to Emma’s curiosity in immunology. [00:06:54] Ken asks whether if it’s that she was paid to stand out in the bush so that mosquitos could feast upon her during a research trip to Tanzania. [00:08:16] Ken asks if Emma’s experience in Africa was limited to mosquitos or if she was able to see some of the impressive wildlife there. [00:09:26] Emma discusses her experiences after her research trip to Africa and her decision to pursue work in immunology at Dr. William Harnett’s lab at the University of Strathclyde. [00:10:32] Dawn asks about the research Emma did in Harnett’s lab. [00:11:46] Dawn mentions that Emma had the opportunity to attend a conference in Philadelphia where she met many interesting people. She goes on to ask about the conference and how she ended up spending the next five and a half years at the University of Pennsylvania. [00:13:52] Dawn mentions another conference Emma was able to attend, this one in California, where she stood out for asking so many questions. Dawn asks about how this led her to go to work at University of California, Riverside. [00:16:50] Ken mentions that the primary focus of Emma’s research at Riverside is the immune response in the brain following Toxoplasma gondii infection, further mentioning that in an episode of the podcast “This Week in Parasitism” Dr. Dickson Despommier referred to Toxoplasma gondii as the most successful parasite on Earth. Ken asks Emma to give an overview of what Toxoplasma gondii is and does. [00:18:58] Dawn asks why Toxoplasma gondii has such a high infection rate in countries such as France and Brazil, where close to 80 percent of people are infected. In the U.S., only 15 to 30 percent of people are infected. [00:20:49] Ken mentions that Eskimos, who’s traditional diet is rich in raw meat, have an almost 100 percent infection rate. [00:21:19] Ken asks how the Toxoplasma parasite prevents digestion in the stomach. [00:23:12] Emma discusses how most cases of Toxoplasma in healthy adults present little to no consequences of infection, but that congenitally infected children or people who are immunocompromised can have serious consequences. [00:25:33] Ken asks how an immunocompetent individual keeps the infection at bay and if there is any risk associated with that constantly active immune response in the brain to this infection. [00:27:32] Ken explains that cats are the only definitive host of the toxoplasmosis parasite because it can only complete its sexual reproduction cycle in the gut of a cat. He goes on to explain that cats eat rats, and sometimes rats eat cat feces, which infects the rats with Toxoplasma gondii, When the cats eat these rats the cats perpetuate the cycle. Ken asks Emma to explain how the infection changes the fundamental fear response in rodents that they naturally have to cats. [30:48] Ken mentions amazing videos on the web showing infected mice approaching cats and rubbing up against them affectionately. [00:31:50] Dawn asks if vegetarians are safe from Toxoplasma gondii infection, given that humans typically contract the parasite via uncooked meat from intermediate hosts such as sheep, cows, goats, and pigs. [00:33:03] Dawn asks if the relationship between the toxoplasmosis parasite and their host can be mutually beneficial. [00:34:24] Dawn asks if seafood can lead to infection. [00:35:33] Ken mentions that there is presently no vaccine for Toxoplasma gondii; however, there are commonsense preventative measures such as pregnant women avoiding cat litter and wearing gloves while gardening. Ken goes on to ask if there are any other ways to reduce chances of infection. [00:37:42] Dawn mentions that Emma and her colleagues at Riverside had a 2016 paper in the journal PLOA Pathogensthat described how Toxoplasma infection leads to a disruption of neurotransmitters in the brain. Dawn goes on to mention that Emma postulated that the infection triggers neurological disease in those who are already predisposed to such diseases. [00:41:45] Dawn asks if the sex of an animal changes the effect of toxoplasmosis. [00:42:36] Ken asks if Emma thinks there would be different effects on animals in the wild, in terms of toxoplasmosis infections, or if the laboratory experiments provide a good model for infection. [00:43:21] Ken mentions that in terms of neurological disease, Toxoplasma’s strongest correlation is with schizophrenia, but Ken mentions that Emma believes the parasite’s presence is a precipitating factor. [00:44:45] Emma explains the arguments for and against the belief that toxoplasmosis infections are asymptomatic in most humans and acts as a silent partner that serves no role. [00:47:01] Dawn asks if we should be looking into the effects of eradicating toxoplasma in asymptomatic humans, and, if so, how would this be accomplished. [00:48:04] Dawn mentions that there are some reports that humans who display risk-taking behavior are more likely to be infected with Toxoplasma gondii, including a higher likelihood in individuals who die in motorcycle accidents as well as entrepreneurs. Dawn asks if there is sufficient evidence to suggest that Toxoplasma gondii might alter risk taking behaviors in humans. [00:49:42] Dawn brings up that after the aforementioned 2016 paper was published, Emma was quoted as saying that for the first time it has been shown that the direct disruption of a major neurotransmitter in the brain resulted from the infection. Dawn asks Emma if her research has since then been focused more on the mechanisms of the parasite. [00:53:07] Ken mentions that in 2016, Sugden et al published results of a study looking at a cohort of early middle-aged individuals that suggested Toxoplasma gondii infection does not result in increased susceptibility to neuropsychiatric disorders, poor impulse control or impaired neurocognitive ability. In addition, they found no association between infection and aberrant personality types. He asks why these findings do not reflect other contemporary research on Toxoplasma gondii. [00:56:12] Dawn asks about Emma’s collaboration with Michael White, with whom she is looking at Toxoplasma gondii cyst formation. [00:57:49] Emma discusses the findings of her2017 paper “Brains and Brawn: Toxoplasma Infections of the Central Nervous System and Skeletal Muscle” in which she discussed how Toxoplasma infection can affect skeletal muscle. [00:59:04] Dawn asks if these effects related to skeletal muscle also occur in people who are asymptomatic. [01:00:47] Ken asks if there might be a way to mitigate the impact of acute and chronic Toxoplasma gondii infection via dietary manipulation or supplementation. Ken referenced a 2016 paper published in PLOS One, in which a Chinese research team reported that T. gondii seems to hijack the host’s PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. Ken said that he wonders if a ketogenic diet or supplementation with exogenous ketones might be beneficial? [01:02:37] Dawn asks what the future of Toxoplasma research should look like given that the broad impact of Toxoplasma gondii on international society and economics is poorly understood. [01:04:22] Ken mentions that in reference to Toxoplasma gondii, there were a whole spat of papers that sensationalized the nature of the infection. He goes on to ask what responsibility should university press offices and the researchers themselves have in preventing clickbait and communicating science effectively. [01:06:58] Dawn mentions that when Emma moved to Riverside she decided to focus on work and not getting into a relationship, but despite this ended up getting married and now has a busy household. [01:07:57] Dawn mentions that when Emma became pregnant her husband took care of the cat litter. Dawn asks if he still changes the cat litter today. [01:08:19] Dawn asks if Emma has any other final words of advice for people trying to avoid Toxoplasma gondii infection.
Links:
Emma Wilson UC Riverside faculty page
Episode 92: Megan Roberts discusses the potential of a ketogenic diet to extend healthspan and lifespan
Our guest today is Megan Roberts, a research scientist who conducted an interesting study that showeda ketogenic diet extended the longevity and healthspan of adult mice. This study has been discussed in several earlier episodes of STEM-Talk.
Megan conducted her research while earning a master’s degree in nutritional biology at the University of California, Davis.
Today, she is the scientific director at Nourish Balance Thrive, an online health-coaching company where Megan helps people optimize their heath and performance.
Show notes:
[00:02:53] Dawn begins the interview mentioning that Megan grew up in Northern California and asks Megan what she was like as a child. [00:03:20] Megan talks about how her interest in science started. [00:03:38] Dawn asks Megan how she became a martial arts instructor, teaching teen-agers as well as children as young as five years old. [00:04:02] Megan talks about her decision to attend the University of California, Davis. [00:04:16] Megan explains why she initially want to major in biochemistry, but decided toward the end of her freshman year to switch majors. [00:04:42] Ken asks Megan about her decision to stay at UC Davis to earn a master’s degree in nutritional biology. [00:05:08] Megan talks about the privilege of having open-minded professors and peers who were a part of her nutritional biology program at UC Davis. [00:06:07] Ken mentions that part of Megan’s thesis ended up in Cell Metabolism, in the form of a paper titeld, “A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.”The paper, Ken points out, has been discussed in several episodes of STEM-Talk. He asks Megan about the motivations behind her study. [00:07:41] Megan describes the three different diets used for the mouse studies. [00:08:30] Dawn mentions that an important aspect of the study was that all of the mice were fed the same number of calories every day. She asks Megan to explain the significance of this parameter. [00:09:23] Megan describes the various markers of physiological function that were measured how the study yielded interesting results in terms of healthspan in the mice. [00:10:14] Dawn asks how the memories of the mice were tested. Dawn also asks Megan to go into detail on the finding that mice on the ketogenic diet were having their memories preserved for longer. [00:11:13] Ken asks Megan how she tested the grip strength of mice. [00:12:05] Megan talks about the two areas of healthspan that saw the most dramatic effects with the ketogenic diet: memory and the preservation of motor-function. [00:12:39] Ken asks if Megan and her colleagues were surprised by the finding that lifespan was increased by 14 percent in the mice fed a ketogenic diet. [00:13:08] Dawn mentions that the ketogenic diet came out on top in the study, followed by the low-carb diet. Dawn mentions that those mice on the low-carb diet, however, surprisingly gained weight asks Megan is she was surprised by this. [00:14:35] Ken asks what lead Megan to the idea of studying the ketogenic diet as an intervention in midlife, as opposed to being a habit throughout life. [00:15:27] Dawn asks how well Megan thinks these mouse models are likely to translate to humans. [00:17:05] Ken asks what experiments Megan would have done to extend her findings reported in the Cell Metabolism paper if she had managed to have more time, funding and resources. [00:17:52] Dawn mentions that Megan’s study suggests that the metabolic changes that accompany carbohydrate restriction might indeed help increase lifespan. However, Dawn asks Megan about ketone bodies themselves (AcAc and BhB) and their potential role in the extension of healthspan. [00:18:13] Ken asks about Megan’s findings in regards to a tissue dependent mTORC1 signaling, in the context of skeletal muscle and the ketogenic diet. [00:20:26] Dawn asks Megan for her take on the tissue specific effects of ketones that she observed in her work. [00:21:12] Megan explains the effects of the ketogenic diet on insulin sensitivity. In her study, the ketogenic diet did not impair insulin sensitivity while the low-carb diet did. [00:22:55] Megan explains the key differences in the design and interpretation of her study versus a similar paper from Eric Verdin’s group, which reported that a cyclical ketogenic diet, but not a consistent one, improved healthspan in older mice. [00:24:13] Dawn asks Megan about her thoughts on the enrichment of a standard diet with exogenous ketones, and if there could be healthspan benefits from that. [00:24:47] Ken mentions a recent paper by Poffé, which suggested that a ketone ester can help prevent some of the negative effects of “over-reaching” in endurance training. [00:25:55] Ken asks if exogenous ketones have their most important effects when taken post-exercise, rather than pre-exercise. [00:27:02] Dawn asks if there are other untapped uses of endogenous or exogenous ketosis that people may not be considering. [00:27:39] Dawn asks Megan what her thoughts are on the communication and interpretation of science of this nature in the public domain, and what responsibilities she feels that university press officers and researchers have in this process. [00:29:34] Dawn mentions that Megan has taken over as chief scientific officer at Nourish Balance Thrive from Tommy Wood, who was interviewed on episode 47 and episode 48 of Stem-Talk. She asks what has led her to decide on her current career and why she has chosen to stay working with athletes as opposed to continuing graduate or medical school. [00:31:16] Megan explains what she does as a health coach. [00:31:45] Dawn asks if the general public could benefit from health coaching [00:32:57] Ken mentions the explosion of research and interest into the gut microbiome and recommends episode 20 of STEM-Talk, an interview with Alessio Fasano, as a primer. Ken then asks Megan about her own quest to recover her gut health, which she has discussed on the Nourish Balance Thrive podcast. [00:35:31] Dawn asks about Megan’s black-and-white, “type A” personality that can sometimes get her into trouble as a fitness enthusiast. [00:36:04] Megan talks about her recent article titled, “Why Your Diet Isn’t Working: Under Eating and Overtraining.” [00:40:00] Ken mentions the blood chemistry calculator project that Megan is working on with Tommy Wood, which uses machine learning algorithms to predict things that are going on biochemically in people based on blood chemistry. [00:41:43] Megan talks about what her exercise regime and diet look like today. [00:42:40] Dawn asks about Megan’s first conversation with Tommy Wood, which was about why eating like a Sumo Wrestler was the best way to gain weight.Links:
Nourish Balance Thrive archives
Episode 91: Irina and Michael Conboy explain tissue repair and stem-cell rejuvenation
Our guests today are Drs. Irina and Michael Conboy of the Department of Bioengineering at the University of California Berkeley. In their lab at Berkeley, the Conboys investigate the process of tissue repair in the body in an effort to determine why damaged tissues do not productively repair as the body ages.
In today’s interview, you will hear the Conboys talk about their early research and a fascinating technique they pioneered called heterochronic parabiosis, where the couple took a young mouse and an older mouse and sutured them together so the animals blood and organs. The Conboys found that the older mouse benefited from this fusion, its aged stem cells becoming rejuvenated and its muscle tissues becoming functionally younger.
Since then, the Conboys’ follow-up research has provided fascinating insights into stem-cell niche engineering, tissue repair, and stem-cell aging and rejuvenation. In 2015, they published an important study showing that high levels of the protein TGF-β1 impaired the ability of stem cells to repair tissues. While their experiments also showed that giving old animals young blood appeared to have some benefit to old stem cells, the Conboys’ most recent work provides compelling evidence suggesting the more interesting benefits are instead produced by a dilution of harmful signals in old blood.
The research coming out of the Conboy lab has profound implications in terms of postponing the onset of age-related diseases as well as the prevention of such degenerative conditions such as Parkinson’s, Alzheimer’s, osteoporosis and sarcopenia.
Show notes:
[00:03:23] Dawn opens the interview asking Irina about her time as a gymnast in the Soviet Union. [00:03:56] Irina talks about how she became interested in biology. [00:04:36] Michael describes how he was a bit of a nerd who spent a lot of time outdoors as a kid studying bugs. [00:05:29] Ken asks what Michael’s plans were when he started his education at Harvard. [00:06:00] Ken inquires as to what it was about lab work that attracted Michael to the point where he abandoned medical school and focused on research instead. [00:06:56] Irina tells the story of her first overseas visit to Boston and how a female friend of hers had set her up with multiple dates for her visit before her plane had even touched down in the states. [00:09:06] Michael recounts the story of his first time in Moscow, where he asked Irina if she wanted to hang out. [00:10:52] Dawn mentions that after graduating, Michael got a job as a lab tech at Harvard, but eventually moved to Philadelphia to join the lab a friend of his was starting. Michael goes on to explain how he and Irina eventually became professional lab rats together there. [00:13:44] Michael explains how he would likely still be a lab tech if it were not for Irina and her desire to study aging, and how that inspired him to pursue his doctorate at Stanford. [00:15:10] Dawn asks Irina about her pursuit of a Ph.D. at Stamford in auto-immunity in the lab of Patricia Jones. [00:18:30] Dawn asks Irina to explain her discovery that Notch Signaling had the potential to regenerate aged muscle, a discovery she made during her post-doc work at Stamford. [00:21:30] Dawn mentions that Irina finished her post-doc work before Michael did, which allowed her to get work at a competing laboratory. Dawn asks if working at a competing labs created tension between the two of them. [00:24:26] Ken asks Irina what led her to look into reactivating old stem cells and whether that might delay or even reverse the onset of aging. [00:26:00] Michael talks about his inspiration for the parabiosis experiment, which involved two mice, one old and one young, being statured together. [00:30:12] Ken asks what the results of the parabiosis experiment were. [00:31:57] Ken mentions that the 2005 paper in Nature, which documented the findings of the parabiosis experiment, sparked an interesting reaction from the media that included headlines about “baby boomer vampires.” Ken asks the Conboys if they were annoyed with the overly simplistic interpretations of their study’s findings. [00:33:27] Dawn asks about Michael and Irina’s research into finding an inhibitory compound in old blood that turned out to be transforming TGF Beta 1. [00:37:44] Ken brings up Michael and Irina’s 2016 paper, published in Nature Communications,in which they described a new, more definitive, experiment than the parabiosis experiment. This blood exchange experiment, aimed to distinguish whether there was a curative property of young blood, or an inhibitory compound being filtered out of old blood, exchanged only blood between the two animals, rather than all of their organ systems. [00:40:55] Michael explains that those experiments came at a time when funding was drying up for the Conboy’s lab. He talks about how discussions with Aubrey de Grey from the SENS Research Foundation aided him and Irina with their experiments. [00:45:23] Dawn asks why Michael and Irina about their criticism of the company “Ambrosia,” a start up in Florida that claims it can combat aging by infusing plasma from young donors into its customers. [00:47:15] Ken says the coverage of Ambrosia has sparked an interesting question of whether or not young people should store their own blood for future transfusions. He asks if anyone has modeled that in mice. [00:51:46] Dawn wonders if it’s the age of a stem-cell’s environment that is the key. If so, she asks the Conboys if their research and findings are going to discourage the use of cell-based therapies to treat disorders related to aging? [00:52:45] Dawn inquires as to how the Conboy’s and their colleagues in the bioengineering department at Southern Cal are developing “youthful micro-niches” for cell and tissue transplantation. [00:54:11] Ken asks Irina to talk about her group’s 2014 paper published in Nature Communications,that showed that oxytocin in mice is vital for muscle maintenance and regeneration, and that the lack thereof leads to premature sarcopenia. [00:56:37] Irina elaborates on the comment noted by Wendy Cousins in a media piece associated with the previously mentioned paper, where she said that oxytocin could become a viable alternative to hormone replacement therapy as a way to combat the symptoms of both male and female aging. [00:58:03] Dawn notes off-label use of intranasal oxytocin is now widely used. Although there have been some human trials of oxytocin associated with mental disorders such as autism, schizophrenia and dementia, it would seem appropriate to have human trials aimed at the potential for oxytocin to prevent, slow, or ameliorate some of the undesirable consequences of aging. Dawn asks the Conboys if they know of any studies underway looking at oxytocin explicitly in the context of aging in humans? [00:59:43] Ken asks Michael if the intranasal oxytocin would be expected to yield the same benefits in muscle as a subcutaneous injection, or if the dose wouldn’t be sufficient. [01:02:33] Ken notes a variety of ways that aging can be slowed, from oxytocin to fasting, and asks Michael about a multifaceted approach to aging. [01:06:27] Ken mentions that a group working at MIT has reported benefits in mice fed lactobacillus reuteri, which has been found to upregulate oxytocin significantly, and that lactobacillus reuteri counteracts age-associated sarcopenia as well. [01:11:58] Ken asks the Conboys what scientific question they would like to answer if they were given unlimited resources and how would they go about answering it. [00:14:05] Ken asks Irina about a bumper sticker she keeps in her office that says “don’t believe everything you think.” [01:15:30] Dawn mentions that Michael and Irina have been married for more than 25 years and that although they don’t have any children, that someone dropping by their house might likely see “Sesame Street” on the TV. Dawn asks the Conboys about their fondness for “Sesame Street.”Links:
Michael Conboy UC Berkeley page
Episode 90: Dawn and Ken answer listener questions
Ken and Dawn return in today’s podcast to answer more listener questions.
Back at the beginning year, Ken and Dawn hosted their first Ask Me Anything episode. In that episode, they promised not to wait another three years and 83 episodes before once again addressing listeners’ questions.
A steady stream of new questions have poured in since that first Ask Me Anything episode. Today, Ken and Dawn take turns answering questions about exogenous ketones, daily allowances of protein, healthy fats, black holes, long-duration space flights, decompression sickness, the future of AI, sloppy science, and much, much more.
Show notes:
[00:04:13] Dawn starts the episode with a listener question for Ken, which is in regards to the Valter Longo interview, episode 64,and the Stuart Phillips interview, episode 84.The listener became confused about protein intake because Longo said that more than 100 grams of protein a day accelerates aging, while Phillips said that the recommended daily allowance for protein is too low. After going online to get some clarification about the right intake of protein, the listener became even confused and asks if Ken could provide some insight and clarity on the issue. [00:08:40] A listener asks Dawn about her research on exogenous ketones. [00:09:44] A listener wonders if Ken has read the 2017 paper titled, “Is Sociopolitical Egalitarianism Related to Bodily and Facial Formidability in Men,”and if so, to share his thoughts on it. [00:11:52] Dawn reads another question addressed to Ken about the utility of a paper out of Harvard that appeared in February.That paper described an observational epidemiological study showing a strong association between the ability to do pushups and cardiovascular events. [00:14:49] A listener says he has read one of Dr. Ford’s papers criticizing the Turing Test, and wonders why he let Dr. Epstein off the hook during episode 89 of Stem-Talkwhen the topic came up. [00:16:02] Dawn asks another question on behalf of a listener who asks about Ken’s comments on the previous AMA episodewhere he expressed some reservations about canola oil. [00:19:27] Dawn follows up by asking Ken which oils he favors. [00:20:13] Another listener asks Ken about his recent appointment to the National Security Commission on Artificial Intelligence and wonders what the issues the commission is investigating. [00:20:54] A listener asks Ken about the so called “futurist” types who foreshadow a dark future where AI has a doom-and-gloom effect on humanity at large. The listener asks Ken to expand on his brighter and more hopeful vision of the future where AI and intelligent systems help humanity. [00:22:44] Dawn asks Ken about the data gathered by the European Space Agency (ESA) since the launching of the Gaia mission, which is cataloguing the composition, brightness, positions, and directions of stars in the Milky Way. [00:25:13] Dawn is asked about a paper published in late 2018 in the proceedings of the national academy of sciences that was titled, “Space Radiation Triggers Persistent Stress Response, Increases Senescent Signaling, and Decreases Cell Migration in Mouse Intestine.”The paper suggests that space radiation could pose a risk for the gastrointestinal tracts of astronauts [00:28:47] Ken asks Dawn a question about her involvement in a record-breaking freshwater-cave dive. [00:31:01] A listener, asking another diving questions of Dawn, wonders if there are any biological or genetic factors that might influence individual susceptibility to decompression sickness or the bends. [00:33:04] Dawn is asked for her thoughts on what the research community has learned since Gena Shaw’s 2015 landmark paper, “New Study Suggests Brain Is Connected to the Lymphatic System: What the Discovery Could Mean for Neurology.” [00:36:15] Ken asks Dawn if sleeping position has any effect on the ability of the brain’s lymphatic system to flush out metabolic waist. [00:37:02] A listener asks Dawn about a 2019 paper published in the proceedings of the national academy of sciences, titled “Brain Ventricular Changes Induced by Long-Duration Space Flight.” [00:38:16] Ken is asked by a listener to explain the process of photographing a black hole. [00:39:49] Another listener asks Ken, via Facebook, about the future of space exploration, as well as the future of human and machine teaming. [00:41:15] A listener writes to Dawn and asks about her involvement in the NASA and ESA 60-day bedrest study, and if she can explain what it entails. [00:43:53] Dawn asks Ken what he thinks the biggest problems with science are, which prompts Ken to cite Dr. John Ioannidis, who was interviews on episode 77.Ioannidis is a Stanford professor who has been described by “BMJ” as “the scourge of sloppy science.” [00:46:28] Ken is asked about modern technology’s effect on democracy, and if it is feasible to fix the issues that arising. Ken’s answer includes references to his interview with Dr. Robert Epstein, episode 89. [00:48:46] A listener asks Ken about his thoughts on mental health and how one can improve mental health and wellness? [00:51:54] Dawn reads a question posed by a listener about self-reinvention, asking if Ken were to reinvent himself again, what would Ken’s next professional path look like? [00:53:29] Ken asks Dawn the same question, asking if she were to reinvent herself again, what direction would she take? [00:54:48] Dawn asks about Ken’s new bike that was built for him in Wyoming, and what sort of riding he plans to do there? [00:57:43] Ken closes the interview with a final question for Dawn about her past connection with professional hockey.
Episode 89: Robert Epstein reflects on his career and the threat big tech poses to privacy and democracy
Our guest today is Dr. Robert Epstein, a psychologist, professor and journalist who is the former editor of Psychology Today.
Robert is currently a co-founder and the senior research psychologist at the American Institute for Behavioral Research and Technology in Vista, California. He has had a distinguished career as a scientist and journalist researching and writing about advances in mental health, the behavioral sciences, and, most recently, the invisible influence that technology companies have on consumer and political behavior.
Robert is the author of 15 books and has written more than 300 scientific and popular articles. He is the founder of the Cambridge Center for Behavioral Studies. He became well known early in his career for his work on creativity. Since then, he has conducted research on a diverse range of topics such as adolescent-and-adult competency, arranged marriages, sexual orientation, self-control and voter manipulation. He also has also developed a number of unique online competency tests which are annually taken by more than a million people.
Show notes:
[00:03:38] Dawn begins the interview asking Robert about growing up in Connecticut. [00:04:57] Dawn asks if Robert skipped a grade in school, given that he graduated from high school at 16. [00:06:16] Robert talks about his interest in computers in the 60’s, and how his high school was one of the first in the country to even have a computer. [00:07:27] Ken asks about what lead Robert to attend Trinity. [00:08:23] Dawn inquires as to whether Robert knew he was going to major in psychology when he first showed up at Trinity, or if he simply ended up gravitating toward the field. [00:10:14] Robert talks about collecting and analyzing the first ever campus-wide sex survey conducted at Trinity. [00:11:40] Robert explains what he did in the two years between obtaining his bachelor’s degree in 1976 and pursing graduate school. [00:13:07] Dawn asks about Robert’s experience at the University of Maryland Baltimore. [00:13:48] Robert tells the interesting story of how he ended up at Harvard, in part, thanks to the behaviorist B.F. Skinner. [00:15:40] Ken asks how Robert managed to be one of the few people who never had to write a dissertation while at Harvard to obtain his doctorate. [00:20:29] Dawn mentions how, at the time, Robert was becoming well known for his work with Skinner. She points out that many behaviorists at the time were working with chimpanzees and asks why Robert and Skinner were working with pigeons instead. [00:23:49] Dawn mentions that after his work with pigeons, Robert began to study creativity. He explains why he concluded that creativity is an orderly and predictable process that can be learned, rather than something one is simply born with. [00:27:34] Robert talks about how he founded the Cambridge Center for Behavioral Studies after his time at Harvard, and how he took on the role of executive director despite Skinner’s warning to never go into administrative work. [00:29:56] Ken asks about Robert’s time at the Cambridge Center and if all the papers he wrote during that time had a theme, or if they were just in general social-science communication. [00:31:28] Robert discusses his book “Cognition, Creativity and Behavior” which is a book of selected essays that he published in 1996. He discusses the various topics in the collection, ranging from creativity to parenting to artificial intelligence. [00:33:09] Ken asks why, after ten years at the Cambridge Center, Robert moved to the west coast. [00:35:40] Dawn asks about Robert’s research into arranged marriages and his finding that couples in arranged marriages developed a greater affection for each other than those who married for love. She asks him about his view that people can deliberately learn to love each other. [00:40:02] Robert discusses his time at the University of California San Diego where he gave students extra credit for participating in “affection building exercises.” He also explains what these were like and what he learned from them. [00:42:37] Ken asks about Robert’s work on psychological maturity, and his criticism of the “artificial extension of childhood” that is prevalent today. [00:47:43] Dawn asks about a study on sexual orientation that Robert published in 2007 that supported Freud’s position that bisexuality is the human norm. [00:50:53] Dawn mentions a book that Robert coedited called Parsing the Turing Test, which refers to Alan Turing’s philosophical test for machine intelligence in which a human judge engages in a three-way conversation between a machine and a person, and if the judge is unable to differentiate the two, then the machine is deemed intelligent. [00:55:53] Ken mentions that he, Clark Glymour and Pat Hayes provided a running commentary on Turing’s paper for Robert’s book, Parsing the Turing Test.Editor’s Note: Ken deems the Turing Test a silly goal for AI. See his paper published in Scientific American (with Pat Hayes) on this topic.
[00:57:15] Dawn mentions that in 2012, Robert co-founded with a former student The American Institute for Behavioral Research and Technology. It’s goal is promote and conduct research that has the potential to improve people’s wellbeing. She goes on to mention that he is the senior research psychologist at the institute, and asks about a current study he is working on that is the largest sexual orientation study ever conducted. [00:58:43] Ken brings up the issue of online manipulation, which has become a hot topic since the 2016 election. He goes on to mention Robert’s 2015 paper on what is known as the search engine manipulation effect, or SEME. This paper showed, in a series of controlled experiments, that biased search results could easily shift the opinions of undecided voters by maybe 20% or more, and even by 80% in certain demographics. Given that most elections are won by small margins this was a potentially very significant finding, and Ken inquires more into this research. [01:03:08] Dawn mentions that Google was recently fined 1.5 billion euros, which equates to approximately $1.7 billion, by the EU. This was the third time Google was fined by the union for anti-trust violations regarding online advertising. While the EU’s regulatory approach has been criticized as unfairly targeting tech companies, this view is beginning to change. She asks if Robert sees Europe’s approach as a potential global model for tempering the influence of Silicon Valley. [01:06:33] Ken talks about Silicon Valley’s relationship to Washington. [01:08:26] Ken asks about Robert’s development of online monitoring systems for search engines. He goes on to ask about the monitoring system used to monitor what search engine companies showed people while conducting election-related searches in the days leading up to the 2016 and 2018 elections. [01:13:04] Robert explains why government regulation isn’t likely to be successful in combating the influence of large tech companies, particularly in light of Mark Zuckerberg’s op-ed piece for the Washington Post in which he proposed government regulation of the whole internet. [01:16:28] Dawn asks about Robert’s opinion on the new documentary The Creepy Line, which features several interviews with him. [01:18:21] Ken mentions that in our society we are addicted to convenience and it seems that we are willing to trade privacy for convenience every time. [01:19:43] Dawn mention’s Robert’s AIBRT website, on which there are a number of resources and tests ranging from “Parenting a Teen” to “Do You Need Therapy?” and “How Infantilized Are You?” [01:20:49] Ken asks Robert to talk about a 2017 article, in which he provided people 7 simple steps that they could take to guard their online presence. [01:23:53] Dawn closes the interview asking if Robert has any interests or hobbies outside of his work.Links:
Episode 88: Duane Mitchell talks about the uphill battle to treat aggressive brain tumors
Our guest today is Dr. Duane Mitchell, the Phyllis Kottler Friedman Professor in the Department of Neurosurgery at the University of Florida College of Medicine.
He’s also the co-director of the university’s Preston A. Wells Jr. Center for Brain Tumor Therapy and Director of the Brain Tumor Immunotherapy Program.
Duane and Dawn have been friends since their days at Duke University where they served on the Institutional Review Board together. Duane got his medical degree and doctorate at Duke and then joined the faculty, where he spent the next decade before moving to the University of Florida in 2013.
Duane and his team at Florida are among the world leaders in the uphill battle to find ways to treat glioblastoma, an aggressive form of brain cancer that affects about 13,000 Americans annually. It’s the disease that recently took the life of Senator John McCain. People who are diagnosed with glioblastoma typically live for less than two years.
Show notes:
[00:03:00] Duane explains the story behind his “quote of the week” tradition, where every Monday morning he share’s a quote with his colleagues in his research group. [00:03:43] Ken asks if it is true that one of Duane’s favorite quotes comes from Mark Twain: “I have never let my schooling interfere with my education.” [00:04:13] Dawn asks if it is true that by the sixth grade Duane had decided he was going to become a doctor. [00:04:52] Duane talks about his decision to attend Rutgers College. [00:05:37] Duane explains how reading Stephen Rosenberg’s book “The Transformed Cell” heavily impacted him during his time at Rutgers. [00:06:43] Dawn mentions that she and Duane met at Duke University, and how this almost didn’t happen because Duane was originally going to attend another university for med school. [00:07:55] Dawn explains that after receiving his MD and Ph.D. from Duke, Duane went on to serve in numerous faculty positions for the next 12 years. During this time, Duane became known as a trailblazer in the application and research of immunotherapy for cancer, particularly brain tumors. Dawn asks Duane for an overview of the role that immunotherapy plays in the treatment of brain tumors. [00:09:30] Duane explains how in 2013 he joined the faculty at the University of Florida and managed to bring his entire team from Duke with him. [00:10:47] Duane has acquired considerable clinical and translational research experience as a principle investigator on seven first-in-human protocols through FDA approved clinical trials. Dawn points out that at Florida, Duane and his team offer unique clinical options for adult and pediatric malignant brain tumor patients. She asks Duane to explain, in depth, the work that he and his do at Florida. [00:12:11] Duane gives an overview of the types of brain tumor and what some of the more common tumor types are. [00:14:09] Dawn asks why Duane chose to specialize in glioblastoma, or GBM, an aggressive form of brain cancer that kills 15,000 Americans eachyear. [00:15:16] Ken asks what characteristics of GBM make those particular types of tumors so difficult to treat. [00:16:17] Duane talks about the standard of care for these malignant brain tumors. [00:18:36] Dawn asks if immunotherapy is a stand-alone approach for treating brain tumors, or if it is administered in conjunction with standard therapy. She goes on to asks if changes to the immune system through radiation or chemotherapy have a negative effect on immunotherapy. [00:21:20] Dawn asks if recent findings about the nervous system’s immune system, and the new-found interconnectedness between the glymphatic system and the lymphatic system impact immunotherapy approaches for brain tumors. [00:23:02] Ken asks how the immune system is naturally equipped to fight cancer. [00:25:36] Dawn explains that the (PD)-1/PD-L1 pathway, otherwise known as Programmed Cell Death, is an immune resistance mechanism that tumor cells exhibit to dampen immune response. Dawn asks about the efficacy of a new class of immunotherapy drugs called immune checkpoint inhibitors that block these signals and allow immune cells to be more effective in fighting the tumor. [00:28:11] Dawn mentions that Duane is helping to lead a health-organized coalition known as the ReMission Alliance, which is a University of Florida initiative that brings together neuro-oncology experts from institutions across the U.S. and Canada. [00:29:32] Ken mentions stories, both anecdotal and found in the literature, of the ketogenic diet having a beneficial effect in fighting cancer. He asks if Duane has given thought to the role of HDAC, given that BHB is an HDAC inhibitor, and that perhaps in addition to the energetic effects of ketone bodies, another benefit of the ketogenic diet in cancer is its signaling effects. [00:31:17] Ken mentions a recent paper in Nature Communications that describes how Duane and his colleagues at Florida have discovered a new use of stem cells that could clear a revolutionary pathway to make immunotherapy drugs effective in treating brain cancer. [00:33:25] Duane explains how cancer vaccines work. [00:34:39] Duane describes his study investigating personalized brain tumor-targeting vaccines for treatment of pediatric medulloblastoma. [00:35:50] Dawn asks about Duane’s clinical trial using an enhanced vaccine credited with significantly extending the lives of multiple glioblastoma patients. [00:37:36] Ken asks what the survival rates are for glioblastoma. [00:39:20] Heterogeneity, which is to say that is there can be a variety of distinct microenvironments with varying populations of neoplastic cells and collections of tissue-specific resident and recruited stromal cell types, can significantly impact response to immune therapy. Given this, Dawn asks if there is an effective tumor microenvironment on response to immunotherapy. [00:40:56] Duane talks about the mechanics and feasibility of the use of nanoparticles to administer cancer antigens to immune cells by crossing the blood brain barrier. [00:42:26] Ken asks if there are genetic or epigenetic factors that influence immunotherapy response. [00:44:38] Ken asks about the gut microbiome and if it has any influence on response to immunotherapy. [00:46:51] Ken mentions an earlier STEM-Talk Guest who specializes in microbiome, Alessio Fasano, interviewed in episode 20 of STEM-Talk. [00:47:56] Duane talks about what he sees as exciting coming down the line in brain tumor treatment. [00:50:15] Dawn asks about the impact that the National Cancer Act has had on cancer research, and our efforts to reduce cancer mortality in America. [00:52:52] Duane ends the interview with advice for aspiring researchers and physicians.Links:
UF Brain Tumor Immunotherapy Program
Episode 87: Dom D’Agostino reflects on his 10 years of research into ketogenic nutrition
Dr. Dominic D’Agostino returns to STEM-Talk to give Ken and Dawn an update on his research into ketogenic nutrition. Dom was the guest on episode 14 back in 2016 when ketogenic diets didn’t even show up on a list of the top-10 diets that people Googled. Since then, the search term “ketogenic diet” has risen to the top of the list.
In today’s episode, Dom talks about his past 10 years of research into ketogenic diets and what he is learning about the physiological benefits of nutritional ketosis.
Dom is tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine.He also is a research scientist here at IHMC.Throughout his career, Dom has been a researcher with a diverse background in neuroscience, molecular pharmacology, nutrition and physiology.
Show notes:
[00:02:55] Dawn begins the interview mentioning that when she and Ken started hosting STEM-Talk, the ketogenic diet wasn’t on the list of the top-10 most Googled diets of 2015. Today, however, Dawn points that ketogenic diet is number one on the list. She asks Dom if he foresaw sudden mass interest in a ketogenic diet coming. [00:04:12] Ken asks Dom for his thoughts on how the ketogenic diet has went from being very obscure to becoming a household term. [00:06:04] Ken comments on the evolutionary component of the ketogenic diet and how our ancestors must have gone in and out of ketosis based on the availability of food. He also comments on the unique aspect of the ketogenic diet, being that it has an objective measurement, and asks Dom to talk about that. [00:06:59] Dawn comments on the cynicism regarding the ketogenic diet, particularly from nutritionists. She asks Dom to address the criticism and pushback that the ketogenic diet receives from so many nutritionists. [00:10:02] Ken mentions that some fields are resistant to change and new science due to the emotion behind established theories. Dom agrees and then talks about how people, even doctors, are resistant to new data and new science. [00:11:13] Dom talks about the most common misconceptions and overrepresentations of the ketogenic diet. [00:12:54] Ken discusses his dissatisfaction with the term “ketogenic diet” since the word diet implies the mandated consumption of certain food items. He goes on to say that if one is in ketosis, then, by definition, they are doing a ketogenic diet, even though they may be in ketosis because they have been fasting and haven’t eaten anything. Ken and Dom discuss how knowledge about ketogenic nutrition has changed over time and that it is certainly possible to eat an unhealthy ketogenic diet. [00:15:35] Dom and Ken talk about the results of a recent Megan Roberts paper, “A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice,”that showed a 13% increase in the lifespan of the mice along with remarkably improved healthspan. [00:20:26] Dom shares his thoughts on the potential of exogenous ketones in the context of blood glucose regulation. [00:27:07] Ken asks if Dom has been tracking Virta Health, which was founded by Dr. Jeff Volek who was interviewed in STEM-Talk episode 43. Virta Health has been publishing impressive results of its trials that show people reversing type-2 diabetes via a well-formulated ketogenic diet. [00:29:13] Ken adds that the reported numbers from Virta show 60% to 70% of their patients going off their insulin medication or greatly reducing their insulin levels. [00:30:55] Dawn asks about Dom’s experience going underwater for 10 days in participation of a NASA NEEMO mission. She asks him to talk about his personal experience as well as his background in hyperbaric physiology. [00:32:08] Dom discusses his group’s work replicating the experimental design of his original oxygen toxicity work in aged and obese rats. [00:33:35] Dawn briefly describes what oxygen toxicity is, and asks Dom about the first human studies, on which he is serving as a consultant, that are being conducted at Duke University to assess the effect of nutritional ketosis on oxygen toxicity and seizure risk. She points out that the studies that are being run by Dr. Bruce Derrick. [00:36:36] Dom discusses brain energy metabolism, and cerebral metabolism, in the context of ketone bodies. [00:39:23] Dom talks about his group’s research into kabuki syndrome, an epigenetic disorder that causes altered growth and cognitive dysfunction in children. [00:42:02] Dom elaborates on the difference between ketone esters and ketone salts. [00:44:00] Ken asks if there’s any evidence that people experience medical issues as a result of ketone esters or salts. [00:48:02] Dawn asks about the transition into ketosis for women, which appears to be more difficult than it is for men, and whether the use of exogenous ketones would be a good option for women. [00:49:43] Dawn asks if there are any more resources that have been generated on a vegetarian ketogenic diet, since the last time she and Dom discussed it on STEM-Talk. [00:50:41] Ken asks about the differences between a ketone tolerance test and a glucose tolerance test. [00:53:36] Ken discusses how some research suggests that anaerobic athletes such as wrestlers, boxers, and MMA fighters will experience a dip in performance on a ketogenic diet. He asks what the state of research is on this topic, and how such athletes can modify their fueling to obtain the benefits of the ketogenic diet (such as brain protection) while maximizing their performance. [00:56:57] Dom discusses the ketogenic diet in relation to the gut microbiome, and the resolving of long-term GI issues for people who go on the ketogenic diet, as well as the study coming from the Sonnenberg lab at Stanford. [00:59:58] Dom talks about his group’s exploration of an ecological idea of cancer treatment based on the ecological concept of animal extinction. [01:02:37] Dom talks about his collaborative paper, written with his Ph.D. student, Andrew Koutnik, and Brendan Egan, titled, “Anti-catabolic Effects of Ketone Bodies in Skeletal Muscle.” [01:05:11] Dawn asks about Dom’s research on cancer cachexia, and what spurred his interest in this topic. [01:07:05] Dawn asks what targets people should shoot for on a ketogenic diet with regards to their electrolytes, and to describe the signs and symptoms of inadequate electrolytes. [01:09:31] Ken asks what experiences stick out to Dom, as he reflects on the last 10 years of his scientific journey. [01:12:11] Dawn asks about Dom and his wife’s new dog and their farm. [01:14:15] Ken asks about Dom’s fitness routine now that he no longer goes to a gym. [01:16:05] Dawn ends the interview asking if Dom recommends farming and gardening as a way to stay in shape.
Links: